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Dermatology > BULLOUS DISEASES
Fogo Selvagem
Article Last Updated: Mar 27, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Editors: Mark G Lebwohl, MD, Chairman, Department of Dermatology, Mount Sinai School of Medicine; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine; Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
FS, endemic pemphigus foliaceus, PF, Brazilian pemphigus, South American pemphigus, Brazilian PF, desmoglein 1, acantholysis
Background
Fogo selvagem (FS), or endemic pemphigus foliaceus (PF), is an autoimmune, organ-specific blistering disease, in which autoantibodies specific for desmoglein 1 may lead to acantholysis (ie, cell-cell detachment). Desmoglein 1 is a glycoprotein that belongs to the cadherin superfamily (ie, calcium adhesion molecules present in the desmosomal core). Other target antigens are also postulated to be relevant in the pathogenesis of PF. PF is characterized by clinical involvement of healthy-appearing skin that may blister when rubbed, a finding named after Dr Piotr Nikolsky1 who initially described this finding. Six types of PF exist. FS is an endemic form of PF and was formerly known as Brazilian PF because it was originally observed in specific river valleys of rural Brazil. It is also reported in Columbia; El Salvador; Paraguay; Peru; and, most recently, in Tunisia. The epidemiology, age distribution, and human leukocyte antigen (HLA) associations distinguish FS from nonendemic PF. FS is Portuguese for wild fire. The description wild fire refers to photosensitivity and the common symptom of severe stinging or burning that occurs with ultraviolet (UV) exposure. In fact, in patients with PF, exposure to UV-B may induce acantholysis in uninvolved skin. Epidermal exposure to UV light may enhance autoantibody epidermal binding and preferential neutrophil adhesion, which can contribute to acantholysis in endemic PF. Pierre Louis Alphee Cazenave, founder of the first journal dedicated entirely to dermatology, inserted into this journal the first description of PF in 1844 in a 47-year-old woman who consulted him at l'Hopital Saint Louis in Paris for a generalized eruption of several years duration.
See Pemphigus Foliaceus for more specific information on this topic.
Pathophysiology
The precise etiology is unknown, but immunogenetic, immunologic, and environmental factors contribute to its pathogenesis. Immunogenetic factors Familial cases are reported. A strong association between FS and class II HLA antigens exists. In one study, 37 (88%) of 42 patients with FS had one or both of the HLA DR1 and DR4 genes, whereas these genes were evident in only 22 (34%) of the 64 control subjects. The HLA-DR1-Dw20 (DRB1*0102) gene is related to susceptibility to FS, whereas absence of the HLA-DQw2 (DQB1*0201) allele is linked with resistance. A common epitope in the third hypervariable (positions 67-74) of the DRB1 gene is involved in susceptibility to FS. It seems that healthy family members of patients with FS have the dominant allele HLA-DQw2, which may be protective. Thus, susceptibility and resistance haplotypes may exist in people at risk for FS. Environmental factors FS is endemic in certain areas of Brazil (ie, Goias, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Parana, Sao Paulo), and in other parts of Latin America (ie, Paraguay, Colombia, Peru, Bolivia, Argentina, El Salvador, Venezuela). Epidemiologic findings indicate that peasants exposed to black fly bites are 4.7 times more likely to develop FS than those who were not exposed, as indicated by the odds ratio. A recent study performed at an Amerindian reservation in Mato Grosso do Sul, Brazil, revealed the predominance of a certain black fly species, Simulium nigrimanum. A sero-epidemiological study of the Terena reservation of Limao Verde, known to have a high prevalence and incidence of FS, suggested that the environmental antigen or antigens triggering the autoimmune response in FS may be linked to exposure to hematophagous insects.2 Immunologic factors In the 1960s, the presence of anti–immunoglobulin G (IgG) circulating autoantibodies and in situ autoantibodies was described in patients with FS. These autoantibodies were detected by means of indirect and direct immunofluorescence (IF), and intracellular staining was demonstrated within the epidermis. The IgG fraction from FS was shown to be pathogenic by means of passive transfer in BALB/c mice. These animals develop the clinical, histologic, and immunologic features of the human disease within 24 hours after the intraperitoneal injection of human IgG. The predominant IgG subclass in FS is IgG4. FS is mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1.3 A preclinical phase has been described with antibodies to only EC5. One hypothesis is that a component of insect vector saliva triggers an antibody response to EC-5. In susceptible individuals, a response to the EC1-2 domains may subsequently develop by epitope spreading with development of FS.
Frequency
International
The incidence of PF varies depending on the population studied. PF is rare and sporadic worldwide. In contrast to pemphigus vulgaris, no predominance of PF exists in Jews and people of Mediterranean descent. This endemic variety of PF occurs with a high frequency in central and southwestern Brazil and in Colombia. The Terena reservation in Brazil, a recently identified focus, has a prevalence of 3.4% of the population. In endemic regions of Brazil, as many as 50 cases per million persons per year are seen. An endemic focus has been found in Tunisia. Other foci may be present in the Maghreb; one case was described in Morocco. In El Salvador, a similar female and age predisposition may also be present. An outbreak was described in 18 men and 3 women in rural Columbia. All were mestizos with an average age of 44 years (range, 22-82 y). Five were relatives. Most worked as farmers or gold miners.4 In Brazil, patients with FS typically reside within 10-15 km of a river or stream, usually in the path of prevailing winds, as one might anticipate with a flying vector. The most likely candidate is a particular black fly, S nigrimanum, the predominant fly species in endemic but not in nonendemic regions in Brazil.
Mortality/Morbidity
- In young patients with FS, the characteristics of stunted growth and diffuse cutaneous exfoliation are noteworthy. In patients with poorly controlled FS, growth is arrested; this is alleviated by treatment.
- This disorder affects young people in their prime, disrupting their academic and vocational pursuits. Personality changes may be manifested by blunted affect.
- Azoospermia is described in adults who had FS as children; however, some of the drugs used to treat this disease may also be associated with azoospermia.
Race
PF is described in all races.
- In contrast to pemphigus vulgaris, no predominance of PF exists in Jews and people of Mediterranean descent.
- The role of genetic factors is evident in FS, which is strongly associated with some HLA-DRB1 haplotypes, including DRB1*0404, DRB1*1402, DRB1*1406, and DRB1*1401. In France, persons with DRB1*0102 and DRB1*0404 have an increased risk for PF.
Sex
In general, the prevalence of FS in men and women is about equal. However, in the Sousse region of Tunisia, an overwhelming predominance of women seem to be affected.5
- An increased incidence of PF was noted in Tunisian women (6.6 cases per million per year), whereas in Western Europe the incidence of PF is about 0.5-1 case per million women per year.
- The annual incidence of endemic PF among women in the Sousse region of Tunisia peaks at 15.5 cases per million women aged 25-34 years.
- In El Salvador, a similar female and age predisposition may also be present. However, an outbreak was described in 18 men and 3 women in rural Columbia; this male predominance is impressive.
Age
The mean patient age of onset of PF is approximately 50-60 years. However, PF can occur in individuals of any age, from infancy onward. FS affects children and young adults. FS does not seem to cause neonatal FS in children of mothers with FS.
- FS occurs in children and young adults and in their genetically related family members. The mean patient age is about 20-30 years.
- The incidence of endemic PF among women in the Sousse region of Tunisia peaks in those aged 25-34 years. The incidence in genetically related family members does not appear to be increased.
- In El Salvador, a similar age predisposition may be also present. However, in an outbreak in rural Columbia, the average patient age was 44 years (range, 22-82 y).
History
- Patients may describe the burning sensation for which the disorder is named.
- Bullae usually begin on the head, neck, and trunk in a seborrheic distribution.
- Patients may experience an intense burning or itching sensation.
Physical
- The clinical features of FS are identical to those in the classic form of PF (Cazenave).
- The primary cutaneous lesions are superficial vesicles or blisters that rupture easily and leave superficial erosions.
- The Nikolsky sign (ie, epidermal detachment after pressure on perilesional and nonlesional skin) usually is spread acrally.
- The Nikolsky sign emphasizes that physical trauma can shear the pathologic epidermis in PF to produce clinical lesions.
- The erosions can become numerous and have a tendency to generalize.
- In contrast to pemphigus vulgaris, PF involves little or no involvement of the mucous membranes.
- UV exposure may enhance lesions or trigger their development.
- Localized or generalized forms exist.
- Generalized forms may evolve into exfoliative erythroderma and lead to death (rare).
- Occasionally, extensive exfoliative erythroderma develops.
- Hyperpigmented or verrucous lesions may be observed in the course of the disease.
- The primary lesions are small superficial blisters. These flaccid bullae are difficult to find because they are transient and transform into erosions.
- The lesions tend to appear on the central trunk and face (ie, face, scalp, upper trunk) in a distribution similar to that of seborrheic dermatitis.
- Sometimes, atrophic changes of the nails and hair are evident. Burning and local pain may occur with the erosions.
- In some patients, a herpetiform variant is also observed.
- Some patients with PF have the initial features of pemphigus herpetiformis. In Tunisia, this feature occurs in 35% of patients with endemic PF.
Causes
The precise etiology of FS is unknown.
- Familial cases are reported.
- FS is endemic in certain areas of Brazil and in other parts of Latin America.
- Epidemiologic studies indicate that peasants exposed to black fly bites are 4.7 times more likely to have FS than those who were not exposed, as indicated by the odds ratio.
- A recent study performed at an Amerindian reservation in Mato Grosso do Sul, Brazil, revealed the predominance of a certain black fly species, S nigrimanum.
- In 1967, Beutner et al6 first reported the presence of anti-IgG circulating autoantibodies or in situ autoantibodies in patients with FS.
Atopic Dermatitis
Contact Dermatitis, Irritant
Drug-Induced Bullous Disorders
Drug-Induced Photosensitivity
Epidermolysis Bullosa
Epidermolysis Bullosa Acquisita
Erysipelas
Erythema Multiforme
Erythroderma (Generalized Exfoliative Dermatitis)
Glucagonoma Syndrome
Herpes Simplex
Impetigo
Insect Bites
Linear IgA Dermatosis
Lupus Erythematosus, Bullous
Lupus Erythematosus, Drug-Induced
Lupus Erythematosus, Subacute Cutaneous
Pemphigus Erythematosus
Pemphigus Foliaceus
Pemphigus Herpetiformis
Pemphigus Vulgaris
Pemphigus, Drug-Induced
Pemphigus, IgA
Pemphigus, Paraneoplastic
Pseudoporphyria
Seborrheic Dermatitis
Subcorneal Pustular Dermatosis
Other Problems to be Considered
Localized forms - Seborrheic dermatitis, cutaneous lupus erythematosus
Generalized forms - Pemphigus vulgaris
Erythroderma - Other causes of erythroderma (eg, psoriasis, atopic dermatitis, cutaneous lymphomas, drug eruptions)
Lab Studies
- IF testing
- Indirect IF testing of the patient's serum: Intercellular fluorescence in the epidermis (anti-IgG autoantibodies) is observed. Often, a positive relationship between the intercellular fluorescence and the activity of the disease exists.7
- Direct IF of a biopsy sample of perilesional skin: Intercellular fluorescence in the epidermis (anti-IgG or anti-C3 autoantibodies) is observed.
- Immunoblotting: Epidermal extracts have reactivity against desmoglein 1 substrate (160 kd in 33% of the cases).
- Immunoprecipitation
- Bovine desmoglein 1 substrate has (45- or 80-kd fragment) 100% reactivity with FS sera.
- Recombinant desmoglein 1 substrate (rDsg1-His) has 100% reactivity with FS sera.
- The immunoglobulin M antidesmoglein-1 response appears to distinguish Brazilian PF (FS) from other forms of pemphigus. However, immunoglobulin M antidesmoglein-1, which is common in FS patients in their native environment and uncommon in other pemphigus phenotypes, is also infrequent in FS patients who migrate to urban areas.8
- Enzyme-linked immunosorbent assay (ELISA): rDsg1-His has 96% positivity with FS sera. The sensitivity of indirect IF and ELISA in detecting intercellular antibodies in FS was studied.9 ELISA (rDsg1) was found to be slightly more sensitive than indirect IF in detecting circulating autoantibodies. However, no test is 100% accurate in differentiating FS from pemphigus vulgaris. In this study, 4 (12%) of 32 patients with FS (cutaneous diseases only) also had desmoglein-3 antibodies.
- Uninvolved skin may be used for direct IF in the diagnosis of FS. Recent results suggest that any cutaneous region can demonstrate pemphigus antibodies by direct IF.10
- Tzanck smears may reveal acantholytic cells.
Histologic Findings
PF begins with acantholysis of the upper epidermis, which often results in a subcorneal cleft. The subcorneal cleft usually enlarges and detaches without bullae formation, although a bulla may form, with acantholysis at both the roof and the floor.
More established lesions may have acanthosis and mild-to-moderate papillomatosis. Hyperkeratosis and parakeratosis may also be evident, with dyskeratotic cells within the granular layer. A mild dermal lymphocytic infiltrate, often associated with the presence of eosinophils, is observed.
Medical Care
- For patients with severe disease, systemic corticosteroid therapy is the treatment of choice.
- Prednisone (1 mg/kg body weight) is administered as a single daily morning dose until blister formation ceases or the Nikolsky sign disappears.
- After initial control is achieved, the prednisone dose is reduced to about half the initial dose. This reduction is followed by slow tapering to the minimal effective maintenance dose over weeks to months.
- Adjuvant therapy includes the use of immunosuppressants such as azathioprine (1-2 mg/kg body weight until lesions clear; with slow tapering of dose), cyclophosphamide (100-200 mg qd, with a reduction to a maintenance dose of 50-100 mg qd), and mycophenolate mofetil (1.5-3 g/d).
- Therapy for FS is usually less aggressive than that of pemphigus vulgaris because of the lower morbidity and mortality rates.
- In patients with limited involvement, topical glucocorticosteroids may be sufficient.
- In more extensive cases, an aggressive treatment (similar to that of pemphigus vulgaris) is necessary; this treatment includes systemic corticosteroids and immunosuppressants.
- In some cases, coadministration of anti-inflammatory agents such as gold, antimalarials, sulfones, or antibiotics may be useful.
- In some patients with PF, nicotinamide 1.5 g/d and tetracycline 2 g/d is reported to be useful.
- Topical treatment with antibiotics and corticosteroids is beneficial. Potent corticosteroid ointments may be effective with long-lasting lesions.
- In some patients, photoprotection may be helpful because UV-B light may trigger acantholysis and cause the disease to flare.
- Antiacantholytic therapies in patients with pemphigus, using cholinomimetics, indicates that cholinergic drugs may be a promising approach for FS.11
- Plasmapheresis is another therapeutic option.
- Plasmapheresis is indicated for patients with poorly controlled disease or those with high circulating autoantibody titers.
- In some patients, this therapy may decrease the autoantibody titers and favorably influence the clinical outcome, especially in otherwise therapy-resistant PF.
- Plasmapheresis should be used in conjunction with daily cyclophosphamide treatment to reduce a predictable rebound increase in autoantibody synthesis.
- Potential complications, including the need for maintaining venous access, a bleeding tendency, electrolyte shifts, pulmonary edema, fever, chills, hypotension, and septicemia, should be considered.
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. Corticosteroids are used to treat inflammatory dermatosis responsive to steroids. They decrease inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.
| Drug Name | Prednisone (Deltasone, Meticorten, Orasone) |
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| Description | Synthetic adrenocortical steroid with predominantly glucocorticoid properties. May decrease inflammation by reversing increased capillary permeability and suppressing neutrophil activity. |
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| Adult Dose | 60-100 mg or more PO every am to control acantholysis |
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| Pediatric Dose | 0.14-2 mg/kg/d PO divided tid/qid (4-60 mg/m2/d) |
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| Contraindications | Documented hypersensitivity; viral, fungal, connective tissue, or tubercular skin infection; peptic ulcer disease; hepatic dysfunction; GI disease |
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| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use |
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| Drug Name | Clobetasol (Temovate) |
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| Description | Class I superpotent topical steroid. Suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. |
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| Adult Dose | Apply 0.05% cream bid for as long as 2 wk; not to exceed 50 g/wk |
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| Pediatric Dose | <12 years: Not recommended
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; viral or fungal skin infections |
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| Interactions | None reported |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | May suppress adrenal function in prolonged therapy; prolonged exposure or application to intertriginous areas and areas with thin skin may result in cutaneous atrophy |
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Drug Category: Immunosuppressives
These agents inhibit key factors in the immune system responsible for inflammatory reactions.
| Drug Name | Azathioprine (Imuran) |
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| Description | Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, resulting in lower autoimmune activity. |
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| Adult Dose | 100-200 mg PO qd in combination with prednisone |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT) |
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| Interactions | Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and monitor liver, renal, and hematologic function; pancreatitis rarely associated |
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| Drug Name | Cyclophosphamide (Cytoxan, Neosar) |
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| Description | Immunosuppressive agent. May be used as monotherapy or as a steroid-sparing agent. Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. |
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| Adult Dose | 100-200 mg IV qd initially; reduce to maintenance dose 50-100 mg IV qd; give in combination with prednisone 25-50 mg PO |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severely depressed bone marrow function |
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| Interactions | Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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| Precautions | Regularly examine hematologic profile (particularly neutrophil and platelet counts) to monitor for hematopoietic suppression; regularly examine urine for presence of red blood cells, which may precede hemorrhagic cystitis |
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| Drug Name | Mycophenolate mofetil (CellCept) |
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| Description | Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production. |
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| Adult Dose | 1.5-3 g PO qd |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | May elevate levels of acyclovir and ganciclovir; antacids and cholestyramine decreases absorption, reducing levels (do not administer together); probenecid may increase levels; salicylates may increase toxicity |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Increases risk for infection; increases toxicity in patients with renal impairment; caution in active peptic ulcer disease |
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Drug Category: Antibiotics
Antimicrobial agents with anti-inflammatory effects may be used.
| Drug Name | Tetracycline (Sumycin, Achromycin) |
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| Description | Has anti-inflammatory activity. Use in combination therapy with nicotinamide. |
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| Adult Dose | 2 g/d PO in divided doses |
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| Pediatric Dose | <8 years: Not recommended
>8 years: Not established |
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| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
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| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increasing risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last one half of pregnancy through age 8 y) can permanently discolor teeth; Fanconilike syndrome may occur with outdated tetracyclines; may affect enterohepatic circulation of estrogens and thereby reduce effectiveness of oral contraceptives |
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Drug Category: Anti-inflammatories
Dapsone is bactericidal and bacteriostatic against mycobacteria. The mechanism of action is similar to that of sulfonamides in which competitive antagonists of PABA prevent the formation of folic acid, inhibiting bacterial growth.
| Drug Name | Dapsone (Avlosulfon) |
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| Description | Used to control dermatologic symptoms of dermatitis herpetiformis. Can be used for patients with pemphigus, and may be the drug of choice for pemphigus herpetiformis and IgA pemphigus. May be provided as monotherapy or in combination with systemic steroids and immunosuppressants. |
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| Adult Dose | 100-200 mg PO qd |
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| Pediatric Dose | Not established; lower doses than those in adults suggested |
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| Contraindications | Documented hypersensitivity; known G-6-PD deficiency |
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| Interactions | May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, such as pyrimethamine (monitor for agranulocytosis during the second and third mo of therapy); probenecid increases toxicity; trimethoprim with dapsone may increase toxicity of both drugs; concurrent rifampin may significantly decrease levels (increased renal clearance) |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Perform weekly blood counts (first month), then monthly WBC counts (6 mo), then semiannual counts; discontinue if platelet or leukocyte counts significantly decrease or if hematopoiesis occurs; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), and hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or those with conditions capable of producing hemolysis (eg, infection, diabetic ketosis); peripheral neuropathy can occur (rare); phototoxicity may occur with UV exposure |
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Drug Category: Vitamins
Vitamins are essential for DNA synthesis and metabolism of proteins, carbohydrates, and fats, and for normal growth and development.
| Drug Name | Nicotinamide (Vitamin B-3, Niacinamide) |
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| Description | Source of niacin used in tissue respiration, lipid metabolism, and glycogenolysis. Use in combination therapy with tetracycline. |
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| Adult Dose | 1.5 g/d PO |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; active liver disease or unexplained, significant increases in AST and ALT levels; large doses of niacin (especially when administered in a sustained-release form) associated with severe hepatotoxicity; can reactivate ulcers in peptic ulcer disease |
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| Interactions | Cutaneous vasodilation can be a problem if high dose used with peripheral dilators such as nitroglycerin; aspirin taken 30-60 min before first dose of the day may help alleviate prostaglandin-mediated adverse effects of niacin (eg, flushing, itching); clonidine may inhibit niacin-induced flushing |
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| Pregnancy | A - Fetal risk not revealed in controlled studies in humans
|
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| Precautions | Pregnancy category C when used at doses greater than RDA-recommended dose; caution in gallbladder disease or diabetes and patients predisposed to gout; monitor blood glucose level; may increase uric acid levels |
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Further Outpatient Care
- Frequent clinical follow-up is required in patients with active disease.
- Patients should be monitored for disease progression, development of complications such as infections, and compliance with and complications of their medications.
- Some clinicians monitor indirect IF titers to gauge the response to therapy; however, this practice is not universal.
- Patients taking long-term steroids and/or immunosuppressants should be appropriately followed up and monitored. The lowest possible dose of steroids and immunosuppressants should be used to minimize the potential for systemic toxicities.
- Be aware of bacterial, viral, or fungal secondary infections and infestations. Disseminated strongyloidiasis is reported.
Deterrence/Prevention
- In endemic areas, measures to minimize exposure to biting flies and other insect vectors are appropriate. These measures include the use of insecticides, protective clothing, and insect screens.
- In some patients, photoprotection may be helpful because UV-B light may trigger acantholysis and cause the disease to flare.
Complications
- FS itself and its therapy may both cause difficulties for the patient.
- The major complication of FS is impetigo.
- Secondary fungal infections, Kaposi varicelliform eruption, scabies, and disseminated strongyloidiasis may occur.
- Other complications reported in patients with FS include dwarfism, azoospermia, dermatophytosis, warts, and Norwegian scabies. These complications may be related to long-term corticosteroid treatment.
Prognosis
- With therapy, the prognosis is good.
- Most patients respond well.
Medical/Legal Pitfalls
- FS is an occupational and environmental hazard.
- Anyone with PF who is asked to work in an endemic region has an occupational disability because FS impairs his or her ability to work.
| Media file 1:
Generalized form with blisters and crusts on the trunk. |
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Media type: Photo
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| Media file 2:
Immunoprecipitation with the recombinant desmoglein 1. Lane 1 is the result in normal human serum. Lanes 2-7 are findings in sera from patients with fogo selvagem. Lanes 2-7 show the reaction of the sera against the extracellular domain of desmoglein 1. |
 | View Full Size Image | |
Media type: Photo
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Fogo Selvagem excerpt Article Last Updated: Mar 27, 2008
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