Case for diagnosis. Radiotherapy-induced pemphigus vegetans.

A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil and cisplatin and concomitant radiotherapy (6 MeV linear photon accelerator, total dose of 54 Gy), with complete remission. Since forty-five days he presentes a painful perianal and intergluteal erosion with circinate pustular borders. Light microscopy showed pseudoepitheliomatous hyperplasia of the epidermis with microabscesses of inflammatory cells (neutrophils and eosinophils) and acantholytic keratinocytes . Indirect immunofluorescence was positive for IgG, with an intercellular pattern, 1:80 titer. The diagnosis of radiotherapy-induced pemphigus vegetans was established and there was significant regression with oral prednisone (40 mg) and topical betamethasone.

RNA-sequencing of the Nyssomyia neivai sialome: a sand fly-vector from a Brazilian endemic area for tegumentary leishmaniasis and pemphigus foliaceus.

Leishmaniasis encompasses a spectrum of diseases caused by a protozoan belonging to the genus Leishmania. The parasite is transmitted by the bite of sand flies, which inoculate the promastigote forms into the host's skin while acquiring a blood meal. Nyssomyia neivai is one of the main vectors of tegumentary leishmaniasis (TL) in Brazil. Southeastern Brazil is an endemic region for TL but also overlaps with an endemic focus for pemphigus foliaceus (PF), also known as Fogo Selvagem. Salivary proteins of sand flies, specifically maxadilan and LJM11, have been related to pemphigus etiopathogenesis in the New World, being proposed as an environmental trigger for autoimmunity. We present a comprehensive description of the salivary transcriptome of the N. neivai, using deep sequencing achieved by the Illumina protocol. In addition, we highlight the abundances of several N. neivai salivary proteins and use phylogenetic analysis to compare with Old- and New-World sand fly salivary proteins. The collection of protein sequences associated with the salivary glands of N. neivai can be useful for monitoring vector control strategies as biomarkers of N. neivai, as well as driving vector-vaccine design for leishmaniasis. Additionally, this catalog will serve as reference to screen for possible antigenic peptide candidates triggering anti-Desmoglein-1 autoantibodies.

Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of "Fogo Selvagem" Pemphigus Foliaceus.

Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1*3B2B (with the York antigen-encoded by p.1408Met) and CR1*3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1*1 haplotype (with the McCoy antigen - encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383*A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS.

Follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease in association with paraneoplastic pemphigus: study of the tumor and successful treatment.

The authors have successfully treated and monitored a case of paraneoplastic pemphigus in association with follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease. The patient was a 56-year-old female who presented with recalcitrant erosive lichen planus of the oral cavity, tongue, and genital mucosa, along with polymorphous eruptions throughout her body. Histological examination of the cutaneous lesions, indirect immunofluorescence on rat bladder epithelium, and western blot of human keratinocyte proteins identified anti-epidermal antibodies in the patient's serum. Positron emission tomography and computed tomography scans found a mass in her retroperitoneal region. Pathology and immunohistochemistry investigation further corroborated the diagnosis of follicular dendritic cell sarcoma originated from hyaline-vascular Castleman's disease. Complete remission was achieved and the patient has been monitored for four years.

Mupirocin pemphigus-like drug reaction in a dog

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morphofunctional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known asthe most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolinmolecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic withbacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis.Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The maincomplaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbarregions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, theanimal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident inabdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytologicalexamination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth.Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatiblewith canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemictreatment with high dose of prednisolone (1.2 mg kg-1)...(AU)

Follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease in association with paraneoplastic pemphigus: study of the tumor and successful treatment

Abstract The authors have successfully treated and monitored a case of paraneoplastic pemphigus in association with follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease. The patient was a 56-year-old female who presented with recalcitrant erosive lichen planus of the oral cavity, tongue, and genital mucosa, along with polymorphous eruptions throughout her body. Histological examination of the cutaneous lesions, indirect immunofluorescence on rat bladder epithelium, and western blot of human keratinocyte proteins identified anti-epidermal antibodies in the patient's serum. Positron emission tomography and computed tomography scans found a mass in her retroperitoneal region. Pathology and immunohistochemistry investigation further corroborated the diagnosis of follicular dendritic cell sarcoma originated from hyaline-vascular Castleman's disease. Complete remission was achieved and the patient has been monitored for four years.

Mupirocin pemphigus-like drug reaction in a dog

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morphofunctional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known asthe most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolinmolecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic withbacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis.Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The maincomplaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbarregions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, theanimal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident inabdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytologicalexamination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth.Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatiblewith canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemictreatment with high dose of prednisolone (1.2 mg kg-1)...

Manifestación oral del pénfigo vulgar. Reporte de un caso / Oral manifestation of vulgar pemphigus. A case report

RESUMEN El pénfigo es una enfermedad autoinmune potencialmente mortal, que causa ampollas y erosiones en la piel y en la membrana mucosa. Las lesiones epiteliales son el resultado de autoanticuerpos que reaccionan con las glicoproteínas desmosomales y están presentes en la superficie celular del queratinocito. La reacción autoinmune contra estas glicoproteínas causa una pérdida de adhesión celular, resultando en la formación de ampollas intraepiteliales. Del 80 al 90 % de los pacientes con pénfigo vulgar, desarrollan trastornos cutáneos y en el 60 % de los casos alteraciones en la mucosa que es el primer o único signo. El diagnóstico de las lesiones en cavidad bucal es fundamental, ya que pueden prevenir su afectación a la piel. Si se establece el tratamiento en su etapa inicial, la enfermedad es más fácil de controlar y aumenta la posibilidad de una remisión temprana del trastorno y mejor calidad de vida. Este reporte de caso mostró a una paciente de 35 años, la que comenzó a presentar lesiones ulceradas en toda la orofaringe, con sensación de ardor e incapacidad para la ingestión de alimentos. El diagnóstico fue pénfigo vulgar (AU).

ABSTRACT Pemphigus is a potentially deadly autoimmune disease causing blisters and erosions in the skin and the mucous membrane. The epithelial lesions are the result of antibodies reacting to desmosomal glycoproteins, and are present in the keratinocytes cellular surface. The autoimmune reaction to these glycoproteins causes a cellular adhesion loss resulting in the formation of intraepithelial blisters. From 80 to 90 % of the patients with vulgar pemphigus develop skin disorders, and 60 % of the cases show mucosa changes as the first or unique sign. The diagnosis of the lesions in oral cavity is essential because it could prevent the skin damage. If the treatment begins in an initial stage, it is easier to control the disease and the possibility of the disorder's early remission and a better life quality increases. This is the report of the case of a female patient, aged 35 years, who presented ulcerated lesions in the entire oropharyngeal region, with itching sensation and inability for food consumption. The diagnosis was vulgar pemphigus (AU).

Fogo selvagem: endemic pemphigus foliaceus

Abstract: Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.

Paraneoplastic pemphigus associated with chronic lymphocytic leukemia: a case report.

BACKGROUND: Paraneoplastic pemphigus is a rare multiorgan disease of autoimmune causes, usually triggered by neoplasias, mainly of lymphoproliferative origin, such as leukemia and lymphoma. This disorder is categorized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmogleins, desmocollins, and others that exist in cellular junctions. Paraneoplastic pemphigus can manifest clinically in a variety of ways, ranging from mucositis to lesions involving the skin and pulmonary changes. The diagnosis depends on the correlation between the clinical and histopathologic evaluations. Currently, the treatment of this disease is still very difficult and ineffective. The prognosis is poor, and the mortality rate is very high. CASE PRESENTATION: We report a case of a Caucasian patient who had chronic lymphocytic leukemia and developed paraneoplastic pemphigus with severe impairment of skin and mucosa. The initial diagnostic hypothesis was Stevens-Johnson syndrome. The histopathological examination of the skin biopsy was compatible with paraneoplastic pemphigus, and the definitive diagnosis was made on the basis of clinical-pathological correlation. CONCLUSIONS: With the presence of multiorgan lesions in patients with lymphoproliferative neoplasia, paraneoplastic pemphigus should always be considered among the possible diagnostic hypotheses, because diagnosis and early treatment may allow a better prognosis for the patient.

Fogo selvagem: endemic pemphigus foliaceus.

Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.

Pemphigus foliaceus with pustular presentation in a patient with psoriasis.

Pemphigus foliaceus is a chronic autoimmune disease of the skin, clinically characterized by scaly and crusty cutaneous erosions involving the seborrheic areas. The patient can eventually become erythrodermic. There are reports of atypical cases of pemphigus foliaceus with pustules and neutrophils, and clinical differentiation from generalized pustular psoriasis of von Zumbusch is difficult. We report the case of a 55-year-old man with a history of psoriasis vulgaris that has developed pemphigus foliaceus with pustules, triggered by withdrawal of systemic corticosteroids. This is the first report associating this atypical form of pemphigus with psoriasis, suggesting that an overlap with generalized pustular psoriasis can occur.

Pênfigo foliáceo em um gato de oito meses de idade: possível reação cutânea adversa a fármacos? / Pemphigus foliaceus in an eight-month-old cat: possible cutaneous adverse drug reaction?

Background: Pemphigus foliaceus is an autoimmune skin disease whose the occurrence in feline clinic is uncommom. The etiology is unknown in most cases. Althought it is a rare condition in cats, pemphigus foliaceus can be induced by drugs. It may affect both adult and old cats with no sexual or racial predilection and diagnosis is based on animal historical, clinical examination and skin histopathology. Moreover, the treatment consists in immunosuppressive-based drugs. This paper describes a pemphigus foliaceus case in an eight-month-old kitten, probably due a cutaneous adverse drug reaction.Case: A 8-month-old, neutered male mongrel cat with crusted lesions located on face was examinated at the Veterinary Hospital. The owners reported that they had adopted the patient two months before the clinical presentation suggesting that this background was unknown. The cat was treated in a local veterinary clinic with antibiotics and anti-inflammatory for rhinotracheitis and herpetic dermatitis on face due to the occurrence of sneezing and crusted pruriginous dermatitis. The kitten presented erosions, purulent exudation and crusts on pinnae, nasal and supra ocular areas, paronychia with purulent exudate and alopecia at distal portion of the tail. Supplementary exams such as skin scraping, cytology and fungal culture were performed to rule out other agents and confirm the diagnosis. The parasitological and fungal examination resulted negative despite the fact that cytological exam showed coccoid bacteria. Complete blood count and biochemical profile showed no alteration and the test for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) resulted negative. Histological changes were consistent with intra-epidermal pustular subcorneal with acantholysis dermatitis. An immunosuppressive dose of prednisolona was prescribed for 15 days...

Pênfigo foliáceo em um gato de oito meses de idade: possível reação cutânea adversa a fármacos? / Pemphigus foliaceus in an eight-month-old cat: possible cutaneous adverse drug reaction?

Background: Pemphigus foliaceus is an autoimmune skin disease whose the occurrence in feline clinic is uncommom. The etiology is unknown in most cases. Althought it is a rare condition in cats, pemphigus foliaceus can be induced by drugs. It may affect both adult and old cats with no sexual or racial predilection and diagnosis is based on animal historical, clinical examination and skin histopathology. Moreover, the treatment consists in immunosuppressive-based drugs. This paper describes a pemphigus foliaceus case in an eight-month-old kitten, probably due a cutaneous adverse drug reaction.Case: A 8-month-old, neutered male mongrel cat with crusted lesions located on face was examinated at the Veterinary Hospital. The owners reported that they had adopted the patient two months before the clinical presentation suggesting that this background was unknown. The cat was treated in a local veterinary clinic with antibiotics and anti-inflammatory for rhinotracheitis and herpetic dermatitis on face due to the occurrence of sneezing and crusted pruriginous dermatitis. The kitten presented erosions, purulent exudation and crusts on pinnae, nasal and supra ocular areas, paronychia with purulent exudate and alopecia at distal portion of the tail. Supplementary exams such as skin scraping, cytology and fungal culture were performed to rule out other agents and confirm the diagnosis. The parasitological and fungal examination resulted negative despite the fact that cytological exam showed coccoid bacteria. Complete blood count and biochemical profile showed no alteration and the test for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) resulted negative. Histological changes were consistent with intra-epidermal pustular subcorneal with acantholysis dermatitis. An immunosuppressive dose of prednisolona was prescribed for 15 days...(AU)

Pemphigus foliaceus with pustular presentation in a patient with psoriasis

Abstract Pemphigus foliaceus is a chronic autoimmune disease of the skin, clinically characterized by scaly and crusty cutaneous erosions involving the seborrheic areas. The patient can eventually become erythrodermic. There are reports of atypical cases of pemphigus foliaceus with pustules and neutrophils, and clinical differentiation from generalized pustular psoriasis of von Zumbusch is difficult. We report the case of a 55-year-old man with a history of psoriasis vulgaris that has developed pemphigus foliaceus with pustules, triggered by withdrawal of systemic corticosteroids. This is the first report associating this atypical form of pemphigus with psoriasis, suggesting that an overlap with generalized pustular psoriasis can occur.

Update on fogo selvagem, an endemic form of pemphigus foliaceus.

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.