Canine cutaneous lupus erythematosus with prominent interdigital lesions in two greyhounds.

Canine cutaneous lupus erythematosus (CCLE) is a well-described, yet uncommon, autoimmune disease which can present clinically with different variants. This case report describes the clinical and histopathological presentation, and treatment response, of CCLE affecting a novel location, the interdigital skin, in two unrelated greyhounds.

O lúpus eritematoso cutâneo canino (LECC) é uma doença autoimune bem descrita, porém incomum, que pode se apresentar clinicamente com diferentes variantes. Este relato de caso descreve a apresentação clínica e histopatológica, e a resposta ao tratamento, do LECC afetando uma nova localização, a pele interdigital, em dois galgos não aparentados.

El lupus eritematoso cutáneo canino (CCLE) es una enfermedad autoinmune bien descrita, aunque poco frecuente, que puede presentarse clínicamente con diferentes variantes. Este informe de caso describe la presentación clínica e histopatológica, y la respuesta al tratamiento, de CCLE que afecta a una nueva ubicación, la piel interdigital, en dos galgos no relacionados.

Le lupus érythémateux cutané canin (LECC) est une maladie auto-immune bien documentée, mais peu fréquente, qui peut se présenter cliniquement sous différents variants. Ce rapport clinique décrit la présentation clinique et histopathologique, ainsi que la réponse au traitement, du LECC affectant une nouvelle localisation, la peau interdigitée, de deux lévriers non apparentés.

Pharmacology of drugs used in autoimmune dermatopathies in cats and dogs: A narrative review.

Immunosuppressive drugs are the mainstay of treatment for many feline and canine autoimmune skin diseases, either as monotherapy or in combination with other drugs. Treatment with these drugs is often lifelong and may have long-term consequences on the affected animal's overall quality-of-life. Clinicians need to understand the pharmacology of immunosuppressants in planning and executing the treatment regimen for the best possible clinical outcome, as well as reducing the risk of adverse effects. This review paper will focus on the mechanism of action, pharmacokinetics and pharmacodynamics, clinical uses and adverse effects of immunosuppressive drugs used to treat autoimmune dermatoses in cats and dogs. These include glucocorticoids, ciclosporin A, azathioprine, chlorambucil, mycophenolate mofetil, oclacitinib and Bruton's tyrosine kinase inhibitors.

Les médicaments immunosuppresseurs constituent la base de la thérapeutique de nombreuses dermatoses auto­immunes félines et canines, soit en monothérapie, soit en association avec d'autres médicaments. Le traitement par ces médicaments dure souvent toute la vie et peut avoir des conséquences à long terme sur la qualité de vie globale de l'animal affecté. Les cliniciens doivent comprendre la pharmacologie des immunosuppresseurs afin de planifier et de mettre en place le plan thérapeutique, afin d'obtenir le meilleur résultat clinique possible et de réduire le risque d'effets indésirables. Cet article de synthèse cible le mécanisme d'action, la pharmacocinétique et la pharmacodynamie, les utilisations cliniques et les effets indésirables des médicaments immunosuppresseurs utilisés pour traiter les dermatoses auto­immunes chez les chats et les chiens. Ces médicaments comprennent les glucocorticoïdes, la ciclosporine A, l'azathioprine, le chlorambucil, le mycophénolate mofétil, l'oclacitinib et les inhibiteurs de la tyrosine kinase de Bruton.

Os medicamentos imunossupressores são a base do tratamento para muitas doenças de pele autoimunes felinas e caninas, seja em monoterapia ou em combinação com outros medicamentos. O tratamento com esses medicamentos costuma durar toda a vida e pode ter consequências a longo prazo na qualidade de vida geral do animal afetado. Os clínicos precisam compreender a farmacologia dos imunossupressores para planejar e executar o protocolo de tratamento para se obter o melhor resultado clínico possível, assim como reduzir o risco de efeitos adversos. Este artigo de revisão será focado no mecanismo de ação, farmacocinética e farmacodinâmica, indicações clínicas e efeitos adversos de medicamentos imunossupressores usados para tratar dermatoses autoimunes em cães e gatos. Estes incluem glucocorticóides, ciclosporina A, azatioprina, clorambucil, micofenolato de mofetila, oclacitinib e inibidores da tirosina quinase de Bruton.

Los tratamientos inmunosupresores son la línea de tratamiento principal en muchas enfermedades autoinmunes de la piel de perros y gatos, bien como monoterapia o en combinación con otros fármacos. El tratamiento con estos fármacos es a menudo de larga duración o de por vida y puede tener consecuencias adversas de larga duración en la calidad de vida de los animales. Los veterinarios clínicos tienen que entender la farmacología de los inmunosupresores durante la planificación y ejecución de los tratamientos para obtener los resultados más beneficiosos y reducir los efectos adversos. Este artículo de revisión está enfocado en los mecanismos de acción, farmacocinética, farmacodinámica, usos clínicos y efectos adversos de tratamientos inmunosupresores utilizados en perros y gatos para tratar dermatopatías inmunomediadas de la piel. Se incluyen glucocorticoides, ciclosporina A, azatioprina, clorambucilo, mofetil micofenolato, oclacitinib e inhibidores de la tirosina quinasa de Bruton.

Inflammatory and Immune-Mediated Myopathies, What Do We Know?

Inflammatory myopathies or myositis encompass diseases characterized by the presence of inflammatory cellular infiltrates, mainly polymorphonuclear cells and/or lymphocytes, in muscle. This is in contrast to most forms of muscle disease characterized by myodegeneration that results in macrophage infiltration. Inflammatory myopathies could have infectious or noninfectious causes. Noninfectious causes consist of primary (genetic, autoimmune) or acquired immune-mediated disease. Focal, multifocal or diffuse, acute or recurrent forms of disease can occur. This article will mainly review immune-mediated myopathies in horses. Myositis directly caused by infection such as Clostridium spp and others will not be discussed here.

Autoimmune Dermatopathies of Horses.

Autoimmune dermatopathies are not common in horses. These autoimmune diseases can be idiopathic or triggered by an antigen such as drugs, vaccines, or neoplasia. The most common one is pemphigus foliaceus, which manifests as a pustular, crusting eruption. Other more common pustular diseases should be ruled out before considering pemphigus. Vasculitis is relatively common in horses and can be triggered by a variety of antigenic stimulations. Systemic lupus and true idiopathic autoimmune vasculitis are very rare in horses. Every effort should be made to reach a final diagnosis, as the prognosis for true idiopathic autoimmune skin diseases is poor.

Programming of metabolic and autoimmune diseases in canine and feline: linkage to the gut microbiome.

Metabolic and autoimmune disorders have long represented challenging health problems because of their growing prevalence in companion animals. The gut microbiome, made up of trillions of microorganisms, is implicated in multiple physiological and pathological processes. Similar to human beings, the complicated microbiome harbored in the gut of canines and felines emerges as a key factor determining a wide range of normal and disease conditions. Evidence accumulated from recent findings on canine and feline research uncovered that the gut microbiome is actively involved in host metabolism and immunity. Notably, the composition, abundance, activity, and metabolites of the gut microbiome are all elements that shape clinical outcomes concerning metabolism and immune function. This review highlights the implications of the gut microbiome for metabolic disorders (obesity, diabetes, and hepatic lipidosis) and autoimmune diseases (inflammatory bowel disease, osteoarthritis, asthma, and myasthenia gravis) in canine and feline animals, providing novel strategies and therapeutic targets for the prevention and treatment of pet diseases.

Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells.

Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.

Palisading granulomatous dermatitis and panniculitis (palisading granuloma) of dogs.

Palisading granulomatous dermatitis and panniculitis is recognized in various cutaneous inflammatory lesions secondary to presumed collagen damage. Cutaneous nodules with a palisading arrangement of histiocytes surrounding foci of collagen degeneration have been clinically termed palisading granuloma in dogs. Study aims were to characterize the cellular infiltrate of canine palisading granuloma and document salient clinical features. Inclusion criteria were met for 36 dogs and encompassed nodular dermal and subcutaneous histiocyte-predominant cellular infiltrates targeting and enveloping collagen fibers/necrotic foci with palisading configurations. Infectious causes were ruled out via standard histochemical stains and/or clinical data. Medical records were reviewed for signalment, clinical features, treatment, outcome, and comorbidities. Immunohistochemistry (IBA1, CD204, E-cadherin) and Masson's trichrome stain were used to assess histiocytic populations and dermal collagen, respectively. The histiocytes had moderate or strong immunolabeling for IBA1 and CD204 in 36/36 dogs (100%) and mild positive immunolabeling for E-cadherin in 3/36 dogs (8%). Alteration of collagen was graded as moderate or strong in 32/36 dogs (89%) and mild in 3/36 dogs (8%). Large breeds predominated with 30/36 dogs (83%) being ≥23 kg. Focal nodules were identified in 31/36 dogs (86%). The head/face were involved in 19/36 dogs (53%) and the extremities in 18/36 dogs (50%). Lesions from the 5/36 dogs (14%) with multiple nodules contained prominent eosinophilic infiltrates. Following excision, there was no evidence of recurrence. In conclusion, palisading granulomas are a distinct, non-neoplastic, histiocyte-predominant inflammatory condition in dogs associated with altered dermal collagen and favorable prognosis.

State-of-the-art review of human autoimmune blistering diseases (AIBD).

Autoimmune blistering diseases (AIBDs) are a heterogenous group of skin conditions, broadly classified into two categories depending on the location of blister formation: intraepidermal blistering in the pemphigus group and subepidermal blistering in the pemphigoid group. Although AIBDs occur in both humans and animals, the arsenal of data for human AIBDs far exceeds those of their animal counterpart. Therefore, the main purpose of this review is to highlight existing knowledge, and recent advances in the diagnosis and management of AIBDs in humans - to serve as a road map for veterinary dermatologists. AREAS COVERED: Recent findings include complement-independent pathways in the pathogenesis of bullous pemphigoid, as well as the role of desmoglein and desmocollin autoantibodies in inducing acantholysis. Systemic glucocorticoids are the mainstay of treatment for AIBDs in humans, yet their long-term use is associated with severe adverse effects and complications, thereby limiting their use. Therefore, researchers have been exploring new and safer alternative therapeutic options for human AIBDs such as anti-CD20 monoclonal antibodies (Rituximab), Bruton's tyrosine kinase inhibitors (BTKi) and neonatal Fc receptor (FcRn) blockers. EXPERT OPINION: Randomised controlled trial (RCT) level evidence show that Rituximab and short-course GC regimes are more effective and safer than traditional GC treatment for human AIBDs. FcRn blockers such as SYNT001 have shown positive results in preliminary phase 2 clinical trials for treatment of human pemphigus; further trials are required. Rilzabrutinib (PRN1008), an orally administered BTKi, has recently completed phase 2 trials in pemphigus and is in a phase 3 RCT in humans.

Les maladies auto-immunes de clivage (AIBDs) est un groupe hétérogène de maladies cutanées, classifiées en deux catégories dépendantes de la localisation du clivage : intra-épidermique dans le groupe pemphigus et sous-épidermique dans le groupe pemphigoïde. Bien que les AIBDs existent chez l'homme et chez l'animal, l'arsenal de données pour les AIBDs de l'homme est bine plus développé que pour l'animal. Ainsi, le principal objectif de cette revue et de mettre en lumière les connaissances existantes et les avancées récentes du diagnostic et de la gestions des AIBDs de l'homme- afin de servir de carte de route pour les vétérinaires dermatologues. ZONES COUVERTES: Des données récentes comprennent les voies indépendantes du complément dans la pathogénie de la pemphigoïde bulleuse, ainsi que le rôle de la desmogléine et desmocolline dans la formation de l'acantholyse. Les corticoïdes (GC) systémiques sont le principal traitement des AIBDs de l'homme, bien que leur utilisation au long court avec effets secondaires sévères et complications, limitent leur utilisation. Ainsi, les chercheurs ont explorés de nouvelles options thérapeutiques alternatives plus sures pour les AIBDs de l'homme tels que les anticorps monoclonaux anti-CD20 (Ritumimab), les inhibiteurs de tyrosine kinase de Bruton (BTKi) et des bloqueurs de récepteur Fc néonataux (FcRn). POSITION DES EXPERTS: Les niveaux de preuves des essais contrôlés randomisés (RCT) montrent que le Ritumimab et les traitements de corticoïdes de courte durée sont plus efficaces et plus surs que les traitements traditionnels de GC pour les AIBDs de l'homme. Les bloqueurs FcRn tels que SYNT001 ont montré des résultats positifs dans les essais préliminaires cliniques de phase 2 pour le traitement du pemphigus de l'homme ; d'autres études sont nécessaires. Le Rilzabrutinib (PRN1008), un BTKi oral, a récemment fini un essai de phase 2 dans le pemphigus et une étude de phase 3 RCT chez l'homme.

Las enfermedades autoinmunes ampulosas (AIBDs, por sus siglas en inglés) son un grupo heterogéneo de afecciones cutáneas, que se clasifican ampliamente en dos categorías según la ubicación de la formación de ampollas: ampollas intraepidérmicas en el grupo de pénfigo y ampollas subepidérmicas en el grupo de penfigoides. Aunque los AIBD ocurren tanto en humanos como en animales, el arsenal de datos para los AIBD humanos supera con creces a los de sus homólogos animales. Por lo tanto, el propósito principal de esta revisión es resaltar el conocimiento existente y los avances recientes en el diagnóstico y manejo de los AIBD en humanos, para que sirva como una hoja de ruta para los dermatólogos veterinarios. ÁREAS CUBIERTAS: los hallazgos recientes incluyen vías independientes del complemento en la patogenia del penfigoide ampuloso, así como el papel de los autoanticuerpos de desmogleína y desmocolina en la inducción de acantólisis. Los glucocorticoides sistémicos son el pilar del tratamiento para los AIBD en humanos, sin embargo, su uso a largo plazo se asocia con efectos adversos graves y complicaciones, lo que limita su uso. Por lo tanto, los investigadores han estado explorando opciones terapéuticas alternativas nuevas y más seguras para las AIBDs humanas, como los anticuerpos monoclonales anti-CD20 (Rituximab), los inhibidores de la tirosina quinasa de Bruton (BTKi) y los bloqueadores del receptor de Fc neonatal (FcRn). OPINIÓN DE EXPERTOS: la evidencia a nivel de ensayos controlados aleatorios (RCT) muestra que los regímenes de Rituximab y GC de ciclo corto son más efectivos y más seguros que el tratamiento GC tradicional para los AIBD humanos. Los bloqueadores de FcRn como SYNT001 han mostrado resultados positivos en ensayos clínicos preliminares de fase 2 para el tratamiento del pénfigo humano; se requieren más pruebas. Rilzabrutinib (PRN1008), un BTKi administrado por vía oral, ha completado recientemente ensayos de fase 2 en pénfigo y se encuentra en un RCT de fase 3 en humanos.

As doenças autoimunes bolhosas (DAIBs) são um grupo heterógeno de dermatopatias, amplamente classificadas em duas categorias, dependendo da localização da formação das bolhas: bolhas intraepidermais no grupo do pênfigo e bolhas subepidermais no grupo penfigoide. Apesar das DAIBs ocorrerem tanto nos humanos quanto nos animais, o arsenal de dados sobre as DAIBs humanas é muito maior que o existente para animais. Desta forma, o principal propósito desta revisão é destacar o conhecimento existente, e os recentes avanços no diagnóstico e manejo das DAIBs em humanos - para servir como um roteiro para os dermatologistas veterinários. ÁREAS ABORDADAS: Os achados recentes incluem vias independentes do complemento na patogênese do penfigoide bolhoso, bem como a função dos autoanticorpos anti-desmogleína e anti-desmocolina induzindo acantólise. Glicocorticoides sistêmicos são a base do tratamento das DAIBs em humanos, apesar de seu uso prolongado ser associado a reações adversas e complicações graves,9R limitando assim o seu uso. Desta forma, os pesquisadores têm explorado novas alternativas terapêuticas mais seguras para as DAIBs humanas, tais como os anticorpos monoclonais anti-CD20 (Rituximab), inibidores de tirosina quinase de Bruton (BRKi) e bloqueadores de receptores Fc neonatais (FcRn). OPINIÃO DO ESPECIALISTA: Evidências de ensaios clínicos randomizados e controlados (RCT) demonstram que o Rituximab e terapias de curta duração com GC são mais eficazes e seguros que a terapia tradicional com GC para DAIBs humanas. Os bloqueadores de FcRn, como SYNT001, demostraram resultados positivos em ensaios clínicos preliminares de fase 2 para o tratamento de pênfigo humano; mais ensaios são necessários. Ensaios de fase 2 em pênfigo com o Rilzabrutinib (PRN1008), um BTKi administrado por via oral, foram concluídos e estão conduzindo os ensaios RCT de fase 3 em humanos.

Open trial of Bruton's tyrosine kinase inhibitor (PRN1008) in the treatment of canine pemphigus foliaceus.

BACKGROUND: Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is one of the most common canine autoimmune skin diseases. OBJECTIVES: To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF. ANIMALS: Four privately owned dogs. METHODS AND MATERIALS: Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC). RESULTS: All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17-33 mg/kg. Anti-DSC-1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog. CONCLUSIONS AND CLINICAL IMPORTANCE: BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.

Sterile granulomatous dermatitis and lymphadenitis (juvenile cellulitis) in adult dogs: a retrospective analysis of 90 cases (2004-2018).

BACKGROUND: It has long been speculated that sterile granulomatous dermatitis and lymphadenitis (SGDL) occurs in adult dogs. However, only three published case reports exist. HYPOTHESIS/OBJECTIVES: To describe clinical presentation, identify breed predispositions, and assess treatment and outcomes of adult dogs with the histopathological diagnosis of SGDL. ANIMALS: Included are 90 dogs with biopsies submitted to a veterinary teaching hospital with a histopathological diagnosis consistent with SGDL, from 2004 to 2018, of which 35 had medical records available for review. METHODS: Data were analysed retrospectively from histopathology submission forms, medical records, surveys and telephone calls. Scoring systems were created to aid statistical analysis of outcomes. RESULTS: Havanese dog (P < 0.0001), Australian shepherd dog (P < 0.0001), Irish setter (P < 0.0001), Dachshund (P = 0.0002), bichon frise (P = 0.0003) and Maltese dog (P = 0.004) were significantly over-represented breeds. The median age at onset was 1,292 days (3.54 years). Dogs up to five years of age were significantly over-represented (P < 0.01). Of 35 dogs with medical records available for review, the median treatment duration was 60 days and the median time to remission 28 days. Remission status was not established for five dogs but the remaining 30 dogs reached remission. Nineteen dogs remained in complete remission. Recrudescence occurred in 11 dogs (median follow-up 60 days). CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows a close parallel in clinical appearance, histopathological results and clinical behaviour, of both adult and juvenile onset SGDL; therefore, SGDL should be considered as a differential diagnosis for dogs of all ages.

Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases?

Mesenchymal stem cells are multipotent cells, with capacity for self-renewal and differentiation into tissues of mesodermal origin. These cells are possible therapeutic agents for autoimmune disorders, since they present remarkable immunomodulatory ability.The increase of immune-mediated diseases in veterinary medicine has led to a growing interest in the research of these disorders and their medical treatment. Conventional immunomodulatory drug therapy such as glucocorticoids or other novel therapies such as cyclosporine or monoclonal antibodies are associated with numerous side effects that limit its long-term use, leading to the need for developing new therapeutic strategies that can be more effective and safe.The aim of this review is to provide a critical overview about the therapeutic potential of these cells in the treatment of some autoimmune disorders (canine atopic dermatitis, feline chronic gingivostomatitis, inflammatory bowel disease and feline asthma) compared with their conventional treatment.Mesenchymal stem cell-based therapy in autoimmune diseases has been showing that this approach can ameliorate clinical signs or even cause remission in most animals, with the exception of canine atopic dermatitis in which little to no improvement was observed.Although mesenchymal stem cells present a promising future in the treatment of most of these disorders, the variability in the outcomes of some clinical trials has led to the current controversy among authors regarding their efficacy. Mesenchymal stem cell-based therapy is currently requiring a deeper and detailed analysis that allows its standardization and better adaptation to the intended therapeutic results, in order to overcome current limitations in future trials.

Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Mycophenolic acid in patients with immune-mediated inflammatory diseases: From humans to dogs.

Mycophenolic acid (MPA), a noncompetitive, selective and reversible inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH), is an immunosuppressive agent that has a long history in medicine. Mechanistically, the inhibition of IMPDH leads to the selective and eventual arrest of T- and B-lymphocyte proliferation. Mycophenolate mofetil (MMF), the first MPA-based product to receive marketing approval over two decades ago, was originally indicated for the prophylaxis of organ rejection in human transplant patients. Given its broad immunosuppressive properties and ability to selectively inhibit lymphocyte division and effector functions, the clinical utility of MPA was subsequently explored in a host of autoimmune diseases. Human clinical studies have shown MPA to be safe and effective and support its off-label administration for immune-mediated diseases such as lupus, myasthenia gravis and atopic dermatitis. MMF became generically available in the United States in 2008, and its clinical utility is increasingly being explored as a treatment option for dogs with immune-mediated diseases. This review summarizes the available literature for MPA pharmacokinetics and pharmacodynamics, and the current status of MPA as a treatment for client-owned dogs diagnosed with immune-mediated diseases.

The role of oclacitinib in the management of ischaemic dermatopathy in four dogs.

BACKGROUND: Ischaemic dermatopathy represents a heterogenous and poorly-characterized canine syndrome that is often refractory to conventional immunosuppression. Janus-kinase inhibitors (JAKinibs) are used for the treatment of various human autoimmune diseases, including dermatomyositis. Oclacitinib is a generally well-tolerated, veterinary-approved, nonselective JAKinib that has therapeutic potential as an immunosuppressant. HYPOTHESIS/OBJECTIVES: To describe four cases of treatment refractory juvenile-onset ischaemic dermatopathy that rapidly and durably responded to oclacitinib administration. ANIMALS: Four mixed-breed dogs, three 9-month-old male littermates and one 6-month-old female, were presented for generalized patchy alopecia, scarring and ulcerative dermatitis. Microscopic skin lesions were consistent with a severe ischaemic dermatopathy. METHODS AND MATERIALS: A complete remission of skin lesions could not be achieved in any dog with glucocorticoids alone, nor when these were combined with adjuvant immunosuppressants. Oclacitinib treatment was then initiated at the dosage of 0.4-0.7 mg/kg twice daily, along with a tapering regimen of oral prednisolone. RESULTS: A full clinical remission was achieved within four weeks of starting this combination therapy, with prednisolone being stopped within eight weeks thereof. Remission was maintained in two dogs with lower doses or dosing frequencies of oclacitinib, whereas the two others required persistent twice daily administration of this JAKinib. CONCLUSIONS AND CLINICAL IMPORTANCE: Oclacitinib was a useful immunosuppressive adjuvant to oral glucocorticoids for the treatment of refractory or severe cases of ischaemic dermatopathy in these four dogs. Such observation warrants further studies of the safety, efficacy and mechanism of action of oclacitinib as an immunosuppressant.

Auto-immune skin diseases in animals: time to reclassify and review after 40 years.

It has been more than 40 years since the dual descriptions of canine pemphigus vulgaris. Over the ensuing four decades, the reports of-mostly canine-novel autoimmune skin diseases (AISDs) have progressed in successive waves separated by long periods of quiescence. This Editorial introduces a series of comprehensive review papers on the various canine and feline AISDs. This collection of articles aims at remediating the current veterinary literature deficiency on this topic by summarizing the key historical, clinical, histological, immunological and treatment characteristics of animal AISDs.

Immune-Mediated Muscle Diseases of the Horse.

In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M protein complexes produces ischemia and complete focal infarction of skeletal muscle and internal organs. In Quarter Horse-related breeds with immune-mediated myositis, an apparent abnormal immune response to muscle antigens results in upregulation of major histocompatibility complex class (MHC) I and II on muscle cell membranes, lymphocytic infiltration of lumbar and gluteal myofibers, and subsequent gross muscle atrophy. Rarely, an inflammatory event results in myositis with subsequent systemic calcinosis characterized by a pathognomonic hyperphosphatemia and high fatality rate. This review presents an overview of these immune-mediated myopathies and highlights clinical and pathological features as well as the suspected pathophysiology.

[Autoimmune diseases in dogs and their impact for breeding programs with special reference of the Nova Scotia Duck Tolling Retriever]. / Autoimmunkrankheiten und deren Bedeutung in der Hundezucht am Beispiel des Nova Scotia Duck Tolling Retriever.

INTRODUCTION: Autoimmune diseases are of considerable importance in dog breeding. An increased risk of diseases with genetic predisposition is present especially in breeds with a limited genetic diversity. Strict breeding regulations and a high degree of self responsibility of the breeders are essential to prevent these diseases. There are only a few DNA tests available for detecting carriers of genes predisposing for autoimmune diseases. In this review, we describe the special situation in the Nova Scotia Duck Tolling Retriever, who has a special predisposition for Systemic Lupus Erythematosus (SLE) and for Immune-mediated Rheumatoid Disease (IMRD), as well as for Steroid-Responsive Meningitis Arteritis (SRMA) and Juvenile Addison's Disease (JADD). In addition a short overview on the pathogenesis of autoimmune disease is presented.

INTRODUCTION: Les maladies auto-immunes ont une signification de plus en plus importante et croissante dans l'élevage de chiens. Les races spéciales avec une base d'élevage étroite et une diversité génétique associée limitée sont prédisposées. Un élevage responsable, visant à exclure des animaux particulièrement prédisposés, permet de contrôler la recrudescence des maladies auto-immunes chez les chiens de race. Actuellement, des tests ADN individuels sont proposés, permettant d'identifier les porteurs de gènes. Cette revue systématique décrit la prédisposition particulière du Retriever de la Nouvelle-Écosse pour le lupus érythémateux disséminé et le rhumatisme à médiation immunitaire, la méningite-artérite sensible aux stéroïdes et le syndrome juvénile d'Addison. Mais avant cela, la pathogenèse des maaladies auto-immunes est présentée resp. récapitulée.

Proteome Dynamics in Biobanked Horse Peripheral Blood Derived Lymphocytes (PBL) with Induced Autoimmune Uveitis.

Equine recurrent uveitis is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for 14 years since the initial experiment. Quantitative data could be acquired for 2632 proteins at all three time points. Profound changes (≥2-fold change) in PBL protein abundance were observed when comparing Day 0 with 15, representing acute inflammation (1070 regulated proteins) and Day 0 with 23 (cessation; 1571 regulated). Significant differences applied to proteins with functions in integrin signaling during active uveitis, involving "Erk and pi-3 kinase are necessary for collagen binding in corneal epithelia," "integrins in angiogenesis," and "integrin-linked kinase signaling" pathways. In contrast, at cessation of uveitic attack, significantly changed proteins belonged to pathways of "nongenotropic androgen signaling," "classical complement pathway," and "Amb2 integrin signaling." Several members of respective pathways were earlier shown to be changed in naturally occurring uveitis, underscoring the significance of these findings here and proofing the value of the induced model in mimicking spontaneous autoimmune uveitis. All MS data have been deposited to the ProteomeXchange consortium via the PRIDE partner repository (dataset identifier PXD005580).

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of ß2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.