Papular urticaria: A review of causal agents in Colombia.

Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries.We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms.Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes.Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Urticaria papular y sus agentes causales en Colombia / Papular urticaria: A review of causal agents in Colombia

Resumen La urticaria papular es una enfermedad alérgica causada por la picadura de insectos, la cual predomina en el trópico. El objetivo de esta revisión fue profundizar en sus aspectos epidemiológicos e inmunológicos, particularmente con base en datos publicados en Latinoamérica. Se hizo una revisión no sistemática mediante la búsqueda electrónica de artículos sobre la epidemiología de la urticaria papular, las características entomológicas de los agentes causales y los mecanismos inmunológicos asociados. Según los diversos reportes de centros médicos de Latinoamérica la urticaria papular es frecuente; el único estudio de prevalencia publicado indica que afecta a una cuarta parte de los niños escolares de Bogotá. Hay información sobre la relación causal entre la exposición domiciliaria a la pulga, la pobreza y la urticaria papular en Bogotá, una ciudad representativa de las altitudes andinas. No hay estudios que indaguen directamente sobre los insectos causales en zonas cálidas, aunque se sospecha clínicamente de los mosquitos Aedes aegypti y Culex quinquefasciatus. En cuanto a su patogenia, se destaca la participación de mecanismos celulares que involucran las células colaboradoras Th2, lo cual explica que sea una condición de hipersensibilidad retardada. El papel de la inmunoglobulina E (IgE) en la urticaria papular no está tan claro. Se desconocen los antígenos derivados de los insectos que causan la enfermedad, aunque se plantea que existen moléculas comunes de reacción cruzada entre los insectos, tales como el alérgeno Cte f 2 en la pulga, y sus homólogos en los mosquitos. La urticaria papular es una condición frecuente en Latinoamérica que debe investigarse en profundidad. La caracterización inmunológica de los componentes moleculares que causan esta condición puede resolver interrogantes sobre su etiología y su patogenia.

Abstract Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries. We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms. Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes. Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Vesicular, ulcerative, and necrotic dermatitis of reptiles.

Vesicular, ulcerative, and necrotic dermatologic conditions are common in captive reptiles. Although these conditions have distinct differences histologically, they are commonly sequelae to each other. This article examines the anatomy and physiology of reptile skin; discusses reported causes of vesicular, ulcerative, and necrotic dermatologic conditions; and reviews various management options.

Vesiculobullous skin reaction temporally related to firocoxib treatment in a white rhinoceros (Ceratotherium simum).

A 40 yr-old female white rhinoceros (Ceratotherium simum) suffered from chronic nail-bed abscesses. Due to worsening of clinical signs, the animal's nonsteroidal anti-inflammatory treatment was switched to firocoxib. Approximately 7 days after this change, the animal developed multifocal vesicles and bullae along the lateral aspects of the thorax and abdomen, the dorsum, and the proximal limbs. Cytology and culture did not identify an infectious etiology. Histologically, the lesions consisted of a severe, subacute vesiculobullous dermatitis with intraepidermal to subepidermal clefting with areas of individual keratinocyte necrosis and minor neutrophilic epidermal infiltrates. These findings are similar to those seen in some drug reactions in people; therefore an adverse drug reaction to the firocoxib was suspected.

An outbreak of pseudocowpox in fattening calves in southern Brazil.

Pseudocowpox virus is a parapoxvirus frequently associated with papulovesicular and scabby lesions on the teats and udders of milking cows and is often transmitted to human beings. An unusual outbreak of skin disease in fattening calves in southern Brazil is described. Fourteen of 17 male cattle (82%), aged 6-48 months, feeding on grass pastures were affected. Animals developed papules, vesicles, and scabby proliferative lesions on the muzzle in a clinical course of approximately 10-15 days. The scabby lesions often presented with exudation and bleeding. Histological examination of mucocutaneous tissue in detached scabs revealed acanthosis with thickening of the corneal layer and premature keratinization (parakeratotic hyperkeratosis). The dermis had multifocal lymphoplasmacytic infiltrates. Electron microscopic examination of scab specimens revealed typical parapoxvirus particles: oval shaped (260 nm × 160 nm), enveloped, and covered with a helical layer. Polymerase chain reaction using a set of pan-parapoxvirus primers for the B2L gene amplified a 590-bp product out of DNA extracted from scabs. Nucleotide sequencing of the amplicons revealed a nucleotide homology of 97% with Pseudocowpox virus and lower homology with other parapoxviruses: Bovine papular stomatitis virus (84%) and Orf virus (94%). A phylogenetic tree based on the B2L sequence was constructed, showing that the virus clustered with Pseudocowpox virus isolates.

Clinical and immunological heterogeneity of canine subepidermal blistering dermatoses with anti-laminin-332 (laminin-5) auto-antibodies.

Laminin-332 (laminin-5) is a basement membrane heterotrimeric protein composed of alpha-3, beta-3 and gamma-2 laminin chains. Laminin-332 polypeptides are targeted by auto-antibodies in human patients with mucous membrane (cicatricial) pemphigoid or, more rarely, subepidermal vesicular diseases that resemble epidermolysis bullosa acquisita (EBA) or bullous pemphigoid (BP). The objectives of this report were to characterize the clinical, histopathological and immunological characteristics of nine dogs with auto-antibodies targeting laminin-332. Immunological investigations consisted of direct immunofluorescence (IF), indirect IF with intact and salt-split canine gingival, and salt-split normal or laminin-332-deficient human skin, immunoblotting with purified human laminin-332 and immunoblotting with recombinant NC1 domain of human collagen VII. All dogs exhibited varying degrees of skin blistering and ulceration associated with microscopic subepidermal vesiculation with or without inflammatory cells. Indirect IF established that circulating IgG auto-antibodies bound the dermal side of salt-split canine lip and human skin. In five dogs, IgG variably recognized the basement membrane of laminin-332-deficient human skin (three dogs negative, two dogs positive). In all nine dogs, IgG auto-antibodies detected purified human laminin-332 by immunoblotting. In two dogs, additional targeting of collagen VII-NC1 was present. These observations establish laminin-332 as a novel basement membrane antigen in dogs with autoimmune blistering diseases with variable clinical phenotypes. The names 'acquired junctional epidermolysis bullosa', 'anti-laminin-332 mucous membrane pemphigoid (MMP)' and 'mixed auto-immune subepidermal blistering dermatosis' are proposed for dogs with clinical signs reminiscent of EBA, MMP or BP respectively.

[Recurrent skin problems in a manatee: the diagnostic approach]. / Recidiverende huidproblemen bij een zeekoe: de diagnostische aanpak.

A 40-year-old manatee was referred with recurrent vesicular and ulcerative dermatosis for the past 15 years. During this period the animal was anorectic and lost weight. Differential diagnoses were formulated on the basis of the history and clinical signs. Skin scrapings, bacterial and fungal culture, cytological examination, blood examination, and histopathological examination of skin biopsies narrowed this list down to autoimmune dermatosis. Despite corticosteroid therapy the symptoms recurred and the animal died. Histopathological examination of post-mortem skin biopsies showed again autoimmune dermatosis, more specifically subepidermal bullous autoimmune dermatosis, as the most probable cause of the skin lesions. Post-mortem examination showed cardiac decompensation and chronic nephritis. It was impossible to estimate the possible contribution of the chronic dermatosis to the cause of death. The purpose of this case report is to show the importance of a systematic work-up of disease in exotic animals.

Isotype determination of circulating autoantibodies in canine autoimmune subepidermal blistering dermatoses.

The three most common canine autoimmune blistering skin diseases (AISBD), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA) have recently been separated based on clinical, histological and immunological grounds. The objectives of this study were to determine the isotype profiles of circulating autoantibodies in these dermatoses. Serum was collected from 5 dogs with BP, 15 with MMP and 11 with EBA. All sera were tested using an indirect immunofluorescence method using salt-split canine gingiva as substrate. Anti-basement membrane IgG autoantibodies were detected in all patients. Among the IgG autoantibodies, IgG1 and IgG4 were encountered most frequently, while IgG2 and IgG3 were uncovered in some dogs. IgE autoantibodies were detected more often than IgA or IgM autoantibodies in any of the three entities. The predominance of IgG1, IgG4 and IgE autoantibody isotypes in dogs with AISBD is very similar to the situation found in humans with the homologous diseases.

Résumé Il a été récemment possible de différencier les trois plus fréquentes dermatoses bulleuses sous-épidermiques (pemphigoide bulleuse [BP], pemphigoïde des muqueuses [MMP] et épidermolyse bulleuse acquise [EBA]) sur la base de critères cliniques, histologiques et immunologiques. Les buts de cette étude étaient de déterminer les profils isotypiques des autoanticorps circulants dans ces maladies. Le sérum de 5 chiens à BP, 15 chiens à MMP et 11 chiens à EBA a été collecté et testé en utilisant une méthode d'immunofluorescence indirecte avec comme substrat une gencive canine clivée par le sel. Des autoanticorps IgG anti-membrane basale ont été détectés chez tous les patients. Parmi ces IgG, les IgG1 et IgG4 étaient rencontrées le plus souvent, alors que les IgG2 et IgG3 étaient absentes chez certains chiens. Des autoanticorps IgE étaient plus fréquemment rencontrés que des IgA ou des IgM pour les trois maladies. La prédominance d'IgG1, IgG4 et IgE chez les chiens présentant une dermatose auto-immune bulleuse sous-épidermique est très semblable à la situation rencontrée chez les patients humains souffrant de maladies équivalentes.

Resumen Las tres enfermedades ampollosas y autoinmunes de la piel más frecuentes en la especie canina, penfigoide bulloso (PB), penfigoide de las membranas mucosas (PMM) y epidermólisis bullosa adquirida (EBA), se han separado recientemente en términos clínicos, histológicos e immunológicos. Los objetivos del estudio fueron determinar el perfil de isotipos de autoanticuerpos circulantes en estas dermatosis. Se tomaron muestras serológicas de cinco perros con PB, 15 con PMM y 11 con EBA. Todos los sueros fueron analizados mediante un método indirecto de immunofluorescencia utilizando separación por NaCl (salt-split) y encía canina como substrato. Se detectaron autoanticuerpos IgG antimembrana basal en todos los pacientes. De los autoanticuerpos IgG, los isotipos IgG1 e IgG4, se hallaron con más frecuencia, mientras que los IgG2 e IgG3 fueron detectados sólo en algunos perros. Autoanticuerpos IgE fueron detectados más a menudo que los autoanticuerpos IgA o IgM en las tres entidades. El predominio de los isotipos de autoanticuerpos IgG1, IgG4 e IgE en perros con enfermedades ampollosas autoinmunes de la piel es muy similar a la situación encontrada en humana con enfermedades homólogas.

Effect of substrate selection on indirect immunofluorescence testing of canine autoimmune subepidermal blistering diseases.

The detection by indirect immunofluorescence (IIF) of circulating antibodies in the serum of dogs with autoimmune subepidermal blistering diseases (AISBD) was regarded for a long time as an unrewarding tool. It was, however, demonstrated in humans that the sensitivity of IIF assays depended on the selection of the substrates used. The effects of substrate selection on IIF tests was thus studied by examining sera from 12 dogs with AISBD tested against 8 different substrates from 3 different normal dogs. Patients with AISBD suffered from bullous pemphigoid (n = 4 sera), mucous membrane pemphigoid (n = 4 sera), and epidermolysis bullosa acquisita (n = 4 sera). Substrates included canine tongue, canine lip, canine dorsal haired skin, and ventral haired skin. The same 4 substrates were also split with salt splitting technique (using 1 M sodium chloride), in order to cleave the basement membrane within the lamina lucida and to expose the targeted antigens. The strength of the specific fluorescence of each slide was scored after processing for IIF testing with anti-canine IgG polyclonal antibody. Other criteria, such as background fluorescence, easiness of the interpretation, and variations within a same substrate, were also assessed. Intact canine lip and canine salt-split lip demonstrated consistently stronger intensity of fluorescence and a better ease of interpretation. We concluded that the performance of IIF tests with such substrates was a reliable tool for the detection of circulating IgG autoantibodies of canine patients with AISBD.

Diagnosing new autoimmune blistering skin diseases of dogs and cats.

Autoimmune blistering skin diseases have been recognized for decades in humans and dogs. In the dog, most of these diseases unfortunately were grouped under the generic denomination of bullous pemphigoid without any confirmation that the autoantibodies targeted bullous pemphigoid antigens. In recent years, advanced diagnostic methods have permitted the recognition of new autoimmune blistering skin diseases in humans and companion-animal species. At this time, the diagnosis of these entities is made by combining clinical signs and results of histopathology. Immunologic methods serve to establish the presence of skin-fixed and circulating autoantibodies that target various epidermal or basement membrane antigens. In this article, salient features of the most common canine and feline subepidermal blistering dermatoses (mucous membrane pemphigold, bullous pemphigold, epidermolysis bullosa acquisita) and new variants of cutaneous lupus (type I bullous systemic lupus erythematosus and vesicular cutaneous lupus erythematosus) are presented.

Spongiotic vesicular dermatitis as a cutaneous reaction pattern in seven horses.

Over a 6-year period seven adult horses of different breeds and genders developed multifocal, exudative, oozing dermatitis characterized histologically by epidermal spongiotic vesicles and perivascular eosinophilic, neutrophilic and mixed mononuclear inflammation. Three horses were pruritic. Systemic disease was not noted. Two horses had a history of recurrent urticaria (hives) and one horse had nodules or welt-type lesions that progressed to exudative, oozing lesions. Interepithelial immunoglobulin (Ig)G was detected by avidin-biotin complex-peroxidase staining, but the pattern of staining was more consistent with epithelial oedema than specific IgG deposition associated with pemphigus. The exudative oozing lesions developed under circumstances suggesting that dermal oedema progressed to intracellular and intercellular epidermal oedema, which in turn progressed to the spongiotic vesicular epidermal lesions.

Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans.

Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering dermatosis that affects human children and adults. In contrast to bullous pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen. An immunologic homologue of LAD in humans was identified in two dogs according to the following criteria: 1) erosive, ulcerative, and crusted lesions seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal clefting present in the basement membrane lamina lucida without inflammation or with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd soluble protein LAD-1. The present study establishes unequivocally the existence of a naturally occurring canine model of LAD of humans.

Bullous systemic lupus erythematosus (type I) in a dog.

In human patients with systemic lupus erythematosus, cutaneous subepidermal blistering can occur because of the production of antibodies specific for basement membrane antigens. This condition is referred to as bullous systemic lupus erythematosus (BSLE). A dog was diagnosed with BSLE because it fulfilled the following criteria: (i) a diagnosis of systemic lupus erythematosus by standard methods; (ii) an acquired, vesicular, erosive and ulcerative eruption; (iii) microscopical subepidermal vesicles with neutrophil-predominant inflammation at the dermo-epidermal junction; (iv) deposition of IgG at the epidermal basement membrane zone; and (v) circulating IgG autoantibodies against type VII collagen. Anti-collagen VII type I-BSLE therefore needs to be considered as a possible differential diagnosis for canine autoimmune subepidermal blistering diseases.