Malignant catarrhal fever in a goat: manifestation of virus-induced erythema multiforme.

Malignant catarrhal fever (MCF), caused by ovine herpesvirus 2 (OvHV2; Orthoherpesviridae, Macavirus ovinegamma2), has sheep as natural hosts. OvHV2 is an important macavirus globally that induces fatal disease in dead-end hosts. Goats, which can be infected subclinically with OvHV2, rarely develop MCF. A 28-wk-old female goat was presented with fever and multifocal crusty skin lesions. Histologic examination of a skin biopsy suggested erythema multiforme (EM), with pyoderma and dermal vasculitis. The doe was euthanized and subjected to postmortem and histologic examination. MCF was suspected and PCR assays for macaviruses were performed, followed by immunohistochemistry (IHC) for OvHV2 latency-associated nuclear antigen (oLANA), RNA in situ hybridization for Ov2.5 mRNA, and IHC to characterize infiltrating leukocytes. The main postmortem finding was severe multifocal ulcerative dermatitis with macrophage- and T cell-mediated arteritis. The latter was also detected in kidney, spleen, heart, and intestinal wall. The PCR assay detected high loads of OvHV2 in tissues. OvHV2 oLANA and Ov2.5 mRNA were expressed within the lesions in leukocytes, endothelial cells, fibroblasts, and/or keratinocytes. Our case confirms that MCF can initially manifest clinically as a skin disease in goats and as EM with confirmed viral etiology.

A retrospective study of the range of cutaneous clinical and histological features of erythema multiforme in five ferrets (Mustela putorius furo).

BACKGROUND: Erythema multiforme (EM) is an uncommon cutaneous reaction pattern characterised by panepidermal keratinocyte apoptosis with lymphocytic satellitosis, and is reported in domestic animal species, livestock and rarely ferrets. HYPOTHESIS/OBJECTIVES: The aim of this study was to analyse the spectrum of cutaneous clinical and histological features in ferrets with EM and to evaluate history and treatment outcomes. ANIMALS: Five client-owned ferrets with biopsy-confirmed EM. MATERIALS AND METHODS: Retrospective review of electronic medical records and histopathological reports from 2002 to 2021. Tissue blocks, haematoxylin and eosin re-cuts, and unstained slides were collected to review EM lesions and evaluate for infectious agents with special stains. Immunohistochemical staining was performed to assess cases for viral pathogens. RESULTS: Panepidermal cytotoxic dermatitis consistent with EM was identified in all cases and involved haired skin in four of five and mucous membranes in one of five ferrets. Skin lesions included variably pruritic alopecia, erythema, scaling, crusts and erosions/ulcerations. Histological features included primarily parakeratotic hyperkeratosis, panepidermal keratinocyte apoptosis, lymphocytic satellitosis and interface dermatitis. Superficial colonisation by bacteria, yeasts or by both was a common finding. Four of five ferrets had concurrent adrenal disease, one of which had resolution of skin lesions with deslorelin acetate treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Awareness of the distinct clinical and histological features is key to the diagnosis of EM in ferrets. Clinical resolution was observed with gonadotropin-releasing hormone agonists in two cases, suggesting that adrenal disease should be ruled out as a potential trigger of EM in ferrets.

Hyperkeratotic erythema multiforme variant in 17 dogs.

BACKGROUND: A new canine subgroup defined as 'old-dog' or 'hyperkeratotic' erythema multiforme (HKEM) with marked hyperkeratosis and parakeratosis has been proposed without any detailed description of larger case series. OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, and histopathological and immunological findings in 17 dogs with HKEM. ANIMALS: Inclusion criteria were the presence of (i) scaly skin lesions with or without crusting; and (ii) microscopic lesions typical of EM (i.e. a panepidermal cytotoxic lymphocytic dermatitis with or without basal keratinocyte apoptosis); and (iii) microscopic ortho- and/or parakeratotic hyperkeratosis affecting the interfollicular epidermis. MATERIALS AND METHODS: Clinical questionnaires and skin biopsies were reviewed. Polymerase chain reactions for epidermotropic viruses and direct immunofluorescence were performed. RESULTS: Various breeds were affected with an over-representation of males in their mid-to-late adulthood (median age 9 years). Generalised skin lesions included multifocal-to-coalescing, linear and annular macules and plaques with erythema and adherent firm crusting. Microscopic lesions were specific for EM and featured prominent superficial epidermal apoptosis with lymphocytic satellitosis and parakeratosis. No drug triggers were identified. Polymerase chain reactions for canine herpesvirus polymerase gene, canine parvovirus and canine distemper virus were negative in all HKEM and canine erosive EM (15 dogs) biopsies. Lesions failed to respond to oral and/or topical antimicrobials. Complete remission of signs was achieved in 9 of 17 dogs (53%) using immunosuppressive regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperkeratotic erythema multiforme (HKEM) is a chronic, persistent and clinically distinctive erythema multiforme (EM) variant that differs from 'classic' vesiculobullous erosive-to-ulcerative EM in dogs.

Successful Treatment With Prednisolone and Mycophenolate Mofetil in a Dog With Recurrent Erythema Multiforme Minor.

A 3-year-old neutered male miniature poodle dog was referred with a 19-month history of unresolved dermatological signs despite long-term treatment. On physical examination, the dog had severe multifocal erythematous non-blanching patches and scales in the ventral trunk. Dermatological examination revealed Malassezia infection. Considering the history, clinical signs, and degree of infection, the possibility of a drug eruption appeared higher than that of Malassezia dermatitis. Therefore, bathing in lukewarm water was performed for 4 weeks without any other treatment, but there was no improvement. Subsequently, treatment for Malassezia dermatitis and differentiation from allergic dermatitis were performed, but there was still no improvement. A biopsy was performed, with the histopathology revealing lymphocytic interface dermatitis with keratinocyte apoptosis. Based on the histopathologic evaluation and clinical signs, the dog was diagnosed with erythema multiforme (EM) minor. Immunosuppressive therapy with prednisolone (1 mg/kg PO, twice daily) was initiated and had a good therapeutic effect. However, the lesion recurred after tapering the prednisolone dose (0.5 mg/kg PO, every other day). Therefore, steroid-sparing agents were added to the prednisolone regimen. Ciclosporin, azathioprine, and human intravenous immunoglobulin were administered in combination with prednisolone. Yet again, the lesion recurred when the dose of prednisolone was tapered to 0.5 mg/kg once daily. Mycophenolate mofetil (20 mg/kg PO, twice daily) was then added to the immunosuppressive regimen as a steroid-sparing agent, and complete remission was achieved and maintained even when the dose of prednisolone was tapered to 0.5 mg/kg every other day. This is the first reported case of recurrent EM successfully treated with a combination of prednisolone and mycophenolate mofetil, and this treatment option should be considered for recurrent EM.

Localised erythema multiforme-like reaction confined to a region of clipper burn in a dog.

Localised erythema multiforme (LEM) is only reported to occur in humans and not in domestic species. This case report describes the clinical and histopathological features of LEM-like reaction in a dog, confined to a region of clipper burn.

L'érythème polymorphe localisé (LEM) n'est signalé que chez l'homme et non chez les animaux domestiques. Ce cas clinique décrit les caractéristiques cliniques et histopathologiques d'une réaction de type LEM chez un chien, localisé sur une région de brûlure de tondeuse.

El eritema multiforme localizado (LEM) sólo se ha descrito en seres humanos y no en especies domésticas. Este artículo describe un caso de un perro con una lesión confinada a una zona de quemadura por un rasurador cuyas características clínicas e histopatológicas fueron similares a LEM.

O eritema multiforme localizado (EML) é relatado apenas em humanos e não em animais domésticos. Este relato de caso descreve as características clínicas e histopatológicas de uma reação EML-símile em um cão, limitada a uma região de queimadura por lâmina de tosa.

Detection of granzyme B in CD3-positive cells infiltrated in lesional skin of a dog with erythema multiforme associated with zonisamide.

In human erythema multiforme (EM), cytotoxic T lymphocytes (CTLs) play an essential role in the pathogenesis. In canine EM, immunohistochemical staining with anti-CD8 antibody using frozen sections has shown the involvement of CTLs; however, CTL infiltration has never been quantitatively analyzed. We herein quantitatively analyzed CTL infiltration by immunohistochemical staining with granzyme B and CD3 antibodies using paraffin sections of a dog with EM associated with zonisamide. The present results indicated approximately 70% of cells at the border between the epidermis and dermis consisted of CTLs. Detection of granzyme B and CD3 using paraffin sections employed in this study can be a clinically applicable method for detecting CTLs.

Erythema multiforme complicated by bacterial folliculitis in a 3-year-old Nubian goat.

Erythema multiforme is a rare hypersensitivity reaction that is reported in several domestic animal species, and not in goats. This case report describes the clinical and histopathological features of erythema multiforme and secondary bacterial skin infection in a goat.

Un érythème polymorphe est une réaction d 'hypersensibilité rare décrite chez plusieurs espèces d'animaux domestiques mais pas chez la chèvre. Cet article décrit les données cliniques et histopathologiques d'un érythème polymorphe et d'une infection bactérienne secondaire chez une chèvre.

El eritema multiforme es una reacción de hipersensibilidad rara que se ha descrito en diversas especies de animales domésticos, pero no en cabras. Este artículo describe las características clínicas e histopatológicas de eritema multiforme e infección cutánea bacteriana secundaria en una cabra.

O eritema multiforme é uma reação de hipersensibilidade rara relatada em várias espécies de animais domésticos, e não em cabras. Este relato de caso descreve as características clínicas e histopatológicas de eritema multiforme e infecção bacteriana secundária da pele em uma cabra.

Presumptive herpesvirus-associated erythema multiforme in a cat.

Erythema multiforme (EM), an uncommon immune-mediated skin disorder of cats, conceivably could be triggered by feline herpesvirus type-1 (FHV-1) infection, in a manner analogous to human herpesvirus-associated EM (HAEM). This report describes a 10-year-old Persian-mixed cat with a presumptive diagnosis of HAEM.

L'érythème polymorphe (EM), est une dermatose à médiation immune rare chez le chat, théoriquement déclenché par une infection FHV-1 (feline herpesvirus type-1), de la même façon que chez l'homme avec HAEM (human herpesvirus-associated EM). Cet article décrit un chat croisé Persan de 10 ans avec un diagnostic présumé de HAEM.

El eritema multiforme (EM), un trastorno cutáneo poco común mediado por el sistema inmunitario de los gatos que posiblemente podría desencadenarse por una infección por herpesvirus felino tipo 1 (FHV-1), de manera análoga a la EM asociada al herpesvirus humano (HAEM). Este informe describe un gato persa mixto de 10 años con un diagnóstico presuntivo de HAEM.

Eritema multiforme (EM), uma doença de pele imunomediada incomum em gatos, em teoria pode ser desencadeada por infecção por herpesvírus felino tipo 1 (FHV-1), de maneira análoga ao EM associado ao herpesvírus humano (EMAH). Este relato de caso descreve um gato persa de 10 anos de idade com diagnóstico presuntivo de EMAH.

Eritema multiforme limitado à cavidade oral em um cão: relato de caso / Multiforme erythema limited to the oral cavity in a dog: case report

O eritema multiforme é uma doença incomum em cães, que afeta pele e mucosas, cuja etiologia ainda não foi completamente elucidada. Contudo, o envolvimento exclusivo da cavidade oral é considerado raro, tendo sido descrito poucas vezes até o presente momento. O objetivo deste trabalho é descrever um caso de eritema multiforme limitado à cavidade oral em um canino. Um cão, fêmea, Akita, com sete anos de idade, apresentou histórico de ulcerações na cavidade oral e nas laterais da língua, sem alterações cutâneas ou sistêmicas. O diagnóstico definitivo foi realizado por meio do exame histopatológico da mucosa oral, e a terapia imunossupressora empregada mostrou-se eficaz. Embora o eritema multiforme seja considerado incomum na espécie canina, este relato de caso apresenta a forma mais rara da doença, com poucos casos descritos em medicina veterinária.(AU)

Multiforme erythema is an uncommon disease in dogs that affects the skin and mucous membranes, the etiology of which has not yet been fully elucidated. However, the exclusive involvement of the oral cavity is considered rare, having been described few times until the present moment. The aim of this work is to describe a case of multiforme erythema limited to the oral cavity in a canine. A seven-year-old female dog, akita, presented a history of ulcerations in the oral cavity and on the sides of the tongue, with no cutaneous or systemic changes. The definitive diagnosis was made through the histopathological examination of the oral mucosa and the immunosuppressive therapy used proved to be effective. Although multiforme erythema is considered uncommon in the canine species, this case report presents the rarest form of the disease, with few cases described in veterinary medicine.(AU)

Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs.

BACKGROUND: Hyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to "classic" erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low. OBJECTIVES: To describe successful treatment of HKEM in two dogs using oclacitinib. ANIMALS: A 7-year-old, spayed Havanese dog (Case 1) and a 1-year-old, intact cryptorchid Dachshund dog (Case 2). METHODS: Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments. RESULTS: Both cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6-0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Oclacitinib could be considered as a fast-acting and effective treatment option for HKEM in dogs.

Erythema Multiforme Major in a Dog Treated with Intravenous Human Immunoglobulin and Immunosuppressive Therapy.

An ∼12 yr old castrated mixed-breed dog was evaluated for a 7 wk progressive history of intermittent hyporexia, lethargy, and erosive dermatitis. Initial examination revealed disseminated papules and macules coalescing to irregularly shaped and serpiginous plaques with widespread erosion progressing to ulceration. Skin histopathology revealed transepidermal keratinocyte apoptosis with lymphocyte satellitosis and lymphocytic and histiocytic interface infiltrate. Histopathology combined with clinical signs and history were compatible with the diagnosis of erythema multiforme major. Treatment was initiated with multidrug immunosuppression. Following 36 hr with no improvement, intravenous human immunoglobulin (0.45 mg/kg IV) was administered resulting in notable improvement in the dog's attitude and appetite within 2 hr and the dog's skin lesions within 48 hr. Following discharge, the dog improved daily with near complete resolution of dermatologic disease achieved 1 mo postdischarge. All immunosuppressive medications were ultimately discontinued 5 mo following presentation. This is the first report of a dog with erythema multiforme major that has been successfully treated with a combination of intravenous immunoglobulin and immunosuppression.

[Targeting the skin - erythema multiforme in dogs and cats]. / Die Haut als Zielscheibe ­ Erythema multiforme bei Hund und Katze.

This review article will describe the complex nature of erythema multiforme in dogs and cats. The disease pattern will be illustrated in terms of etiology, pathogenesis, clinical signs, diagnostics and therapy. Erythema multiforme is a rare, immune-mediated skin disorder with an acute specific reaction pattern of skin and mucous membranes against different underlying causes. Reported triggering factors include drugs, food ingredients and neoplasias, but viral or bacterial infections and vaccine reactions were also identified. In over 20% of the cases the cause cannot be identified. The German Shepherd dog and Pembroke Welsh Corgi seem to be predisposed. Erythematous macules, slightly elevated and peripherally spreading papules as well as circular to arciform patterns were described frequently in the dog. Wheals, plaques, vesicles and bullae that develop into ulcers, are also seen. Frequently affected areas in the dog are the ventrum, mucocutaneous junctions, mouth, pinnae and foot pads. Histopathological findings include single cell necrosis in all layers of the epidermis with lymphocytic satellitosis and a cell-poor interface dermatitis. Elimination of the causative factors and concurrent symptomatic therapy are recommended. The prognosis varies from guarded to fair, depending on the underlying cause, presenting clinical signs and response to therapy.

Erythema Multiforme Associated with Respiratory Disease in a Commercial Breeding Pig Herd.

This study describes an erythema multiforme (EM) in breeding sows, after their mixing in the group housing system. Sows at 30-35 days of gestation showed red and raised skin areas, depression, anorexia, fever, respiratory problems, and increased return to estrus. Blood and nasal samples from diseased sows were examined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay for respiratory pathogens. Hematological and biochemical analyses were performed on the blood samples. From diseased sows, vaginal swabs for microbiological examinations and samples at slaughterhouse for gross and microscopic examinations were collected. Samples from the complete gestation and lactation feed were examined for mycotoxins. All sampled sows were seropositive for Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV). No viremia for PRRSV and porcine circovirus type 2 were detected. All nasal samples were positive for Streptococcus suis, one for Swine Influenza Virus and one for App, Hemophilus parasuis, and S. suis. In all vaginal swabs, Escherichia coli and Streptococcus spp. were detected. Diseased sows had moderate leukocytosis, mild anemia, and thrombocytopenia. No mycotoxins were detected in feed. Histopathological examination revealed increased vascularization of the superficial and middle dermis. EM was likely due to illness caused by viral and bacterial infections. This study suggests that stress caused by the sows' mixing might have triggered the problem.

Erythema multiforme associated with zonisamide in a dog.

This report describes a dog that developed erythema multiforme in temporal association with administration of the sulphonamide-based anticonvulsant drug zonisamide. Similar adverse drug reactions have been associated with sulphonamide antimicrobial drugs. Caution should be exercised when prescribing this medication for dogs with known hypersensitivity to sulphonamides.

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis: a comparative review.

BACKGROUND: Human erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are separate conditions. There is no consensus on classification criteria for the eponymous diseases in animals. RESULTS: Animal EM is very different from 90% of human EM, which is herpes virus associated (HAEM). Animals lack acrally distributed, typical raised targets. Unlike canine parvovirus 'EM', HAEM is not an active infection. Animal EM is often attributed to drugs, but this is rarely proved. Conversely, human and animal SJS/TEN are almost identical, life-threatening disorders of epidermal necrosis and detachment, typically triggered by drugs (occasionally by infectious agents). Both EM and SJS/TEN are mediated by cytotoxic lymphocyte responses against altered keratinocytes (infectious agents or drugs). Apoptosis results from direct cytotoxicity or through soluble mediators, namely Fas ligand, granzymes, perforin and granulysin. Diagnosis in humans is clinicopathological, with emphasis on clinical lesions; histopathology confirms the pathological process as interface (cytotoxic) dermatitis. Human EM is self-limiting; only recurrent and rare persistent cases require antiviral/immunosuppressive therapies. Drug-induced EM responds to drug withdrawal. Idiopathic canine EM (>40%) is usually chronic, refractory to treatment and may represent heterogeneous conditions. Early identification and removal of the causative drug and high-quality supportive care are critical in SJS/TEN. Mortality rate is nevertheless high. CONCLUSIONS AND CLINICAL IMPORTANCE: (1) Histopathological lesions do not reliably differentiate EM, SJS and TEN. (2) A multicentre study to develop a consensus set of clinical criteria for EM and SJS/TEN in animals is overdue. (3) No adjunctive therapies, including intravenous immunoglobulin and ciclosporin, have met evidence-based standards.

Erythema multiforme in a ferret (Mustela putorius furo).

Erythema multiforme, an uncommon skin disease resulting from an aberrant immune response, was diagnosed in a domestic ferret (Mustela putorius furo) based on clinical signs and skin biopsies, and this seems to be the first case report of this dermal disease in the ferret. This article discusses treatment and response, and reviews the small animal literature as it relates to disease pathophysiology and treatment.

Erythema multiforme and epitheliotropic T-cell lymphoma in the oral cavity of dogs: 1989 to 2009.

OBJECTIVES: To describe the clinical signs, major laboratory findings, diagnostic procedures and outcome in dogs with erythema multiforme or epitheliotropic T-cell lymphoma of the oral cavity. METHODS: Retrospective analysis identified 14 client-owned dogs with erythema multiforme or epitheliotropic T-cell lymphoma of the oral cavity. Histological changes were combined with immunohistochemistry and clonality testing data in selected cases, and a clinical follow-up was acquired. RESULTS: Ulcerative stomatitis with no significant or only minor abnormalities on haematology and serum biochemistry panels was common. Histological features were diagnostic in seven cases. The use of immunohistochemistry distinguished the two diseases in an additional three cases. In four cases, the diagnosis remained questionable, and clonality testing for T-cell receptor gamma gene rearrangement helped confirm erythema multiforme in one case. Clinical follow-up revealed erythema multiforme in two and epitheliotropic T-cell lymphoma in one of the remaining questionable cases. CLINICAL SIGNIFICANCE: Erythema multiforme and epitheliotropic T-cell lymphoma may affect, but are rarely limited to the oral cavity of dogs, and they usually present as stomatitis. Histological features alone are not always diagnostic. Immunohistochemistry and clonality testing may assist in the differentiation between the two, but in ambiguous cases, repeated biopsy and clinical follow-up are essential.

Canine parvovirus-2b-associated erythema multiforme in a litter of English Setter dogs.

Erythema multiforme (EM) was diagnosed in a litter of English Setter puppies. The puppies developed erythematous cutaneous lesions at the age of 2 weeks. Microscopically, there was individual keratinocyte apoptosis associated with lymphocyte exocytosis in all layers of the epidermis. Intranuclear viral inclusions were seen in multiple tissues and organs. Tissues from the tongue, lymph node, spleen, skin, and small intestine were positive for Canine parvovirus-2 (CPV-2) and negative for Canine distemper virus (CDV) and Canid herpesvirus 1 by fluorescent antibody test. Negative-staining electron microscopy detected parvovirus particles in the intestinal contents. The skin and small intestine were positive for CPV-2b and negative for CDV by polymerase chain reaction. The mucocutaneous junctions and small intestines stained positive for CPV by immunohistochemistry. The present report documents CPV-2b-associated EM in a litter of English Setters and substantiates the single previous report associating EM with CPV-2. The finding suggests that CPV should be considered as a possible cause of EM in dogs.

Diagnosis of erythema multiforme associated with thymoma in a dog and treated with thymectomy.

A 7 yr old Labrador retriever initially presented for severe halitosis, mild ptylism, and depigmentation of the nasal planum. Erythema multiforme was diagnosed based on clinical signs and dermatopathology. Treatment was initiated but the condition did not resolve. Six months later, the dog was diagnosed with a mediastinal mass. Trucut biopsy was performed and histopathologic diagnosis was consistent with a thymoma. A median sternotomy was performed, the thymoma was excised, and the dog recovered well. Four months postoperatively, there were no longer any obvious erythema multiforme lesions and the skin condition was controlled without medication. Erythema multiforme may be a paraneoplastic disorder associated with thymoma in the dog, similar to thymoma-associated exfoliative dermatitis in the cat. Clinical signs of erythema multiforme may warrant performing thoracic radiographs or thoracic CT to rule out thymoma as an underlying cause.