Clinical and histopathological features of pemphigus foliaceus with and without eosinophilic infiltrates: a retrospective evaluation of 40 dogs

The importance of cellular infiltrates in tissues has been investigated as a diagnostic tool, mechanism of pathogenesis, and prognostic indicator in certain human diseases. Eosinophils, in particular, have a distinct role in the development of cutaneous lesions in human autoimmune diseases. Identification of an eosinophilic infiltrate can aid the diagnosis of immunobullous disease in the early stages of the disease process. In canine pemphigus foliaceus, eosinophils are present to a variable degree within lesional tissue. This study retrospectively evaluated 40 dogs with pemphigus foliaceus, and examined clinical and histologic features and final outcomes in cases with and without eosinophilic infiltrates. Twenty‐five of 40 dogs (63%) had an eosinophilic infiltrate in either the pustules/crust, follicular infundibulum or dermis. There was no statistically significant difference in clinical distribution or appearance of dermatological lesions, response to treatment, or disease outcome in dogs with or without an eosinophilic infiltrate. However, dogs with concurrent disease were significantly more likely to have an eosinophilic infiltrate (P = 0.01). Dogs with adverse effects associated with immunosuppressive therapy were significantly more likely to have an eosinophilic infiltrate (P = 0.05). Fifteen of 40 dogs (38%) had a history of allergic disease and a significantly higher proportion of these dogs had an eosinophilic infiltrate (P = 0.04). An eosinophilic infiltrate was found in more than half of the dogs in this study. These findings justify further studies to investigate the role of eosinophils in the pathogenesis, therapy and prognosis in dogs with pemphigus foliaceus.     

Ultrastructural localization of pemphigus vulgaris antigen on canine keratinocytes in vivo and in vitro

Pemphigus antigens were localized, by use fo immunoelectron microscopy, on canine keratinocytes in vivo on esophageal mucosa and in vitro on established cultured keratinocytes. Convalescent sera from a human being with pemphigus vulgaris and a human being with pemphigus foliaceus reacted with the interdesmosomal cytoplasmic keratinocyte membrane of canine esophagus. Cultured canine keratinocytes expressed the pemphigus vulgaris antigen in a similar pattern, but did not carry the pemphigus foliaceus antigen. The differential presence of cell surface antigens and its relation to various forms of the disease are discussed.     

Pemphigus foliaceus in 91 dogs

A retrospective study of 91 dogs with pemphigus foliaceus was performed. Clinical signs of the disease included crusts (n=79), pustules (n=36), and alopecia (n=33). Lesions were most common on the trunk (n=53), inner pinnae (n=46), face (n=37), and foot pads (n=32). Cytological evaluation revealed acantholytic keratinocytes in 37 of 48 dogs. Results of combination treatment with prednisolone and azathioprine were comparable to results with prednisolone therapy alone. More than half of the dogs achieved remission with appropriate therapy, and another 25% significantly improved.     

Prolonged remission after immunosuppressive therapy in six dogs with pemphigus foliaceus

Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs underwent complete remission, which occurred 1.5-5 months after immunosuppression was initiated, the drugs were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.5-6 years after treatment was stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.     

Immunoperoxidase staining for the detection of autoantibodies in canine autoimmune skin disease; comparison to immunofluorescence results

Skin sections from 22 dogs with autoimmune skin disease were stained with anti-canine IgG, IgM and IgA using an immunobridge immunoperoxidase method. Eight cases of lupus erythematosus, three cases of pemphigus vulgaris, and 11 cases of pemphigus foliaceus were included. Results of previously performed, direct immunofluorescence tests for the detection of canine immunoglobulin on skin were available on 17/22 cases. The immunoperoxidase method yielded an overall positive result in 59% (5/8 lupus erythematosus, 2/3 pemphigus vulgaris and 6/11 pemphigus foliaceus) versus an overall positive result of 47% for direct immunofluorescence (3/5 lupus erythematosus, 2/2 pemphigus vulgaris and 2/10 pemphigus foliaceus). The immunobridge immunoperoxidase method compared favorably to direct immunofluorescence testing of canine skin for autoantibody in cases of lupus erythematosis and pemphigus vulgaris, and was superior in cases of pemphigus foliaceus. This method should prove useful as an aid in the diagnosis of canine autoimmune skin disease.     

Complementary and alternative medicine for neurologic disorders

The use of complementary and alternative veterinary medicine in treating neurologic disorders has increased in popularity in response to advances in human alternative and integrative therapies. Neurolocalization of lesions to the brain, spinal cord, and neuromuscular systems is discussed, as well as the diagnostics and therapeutics used to treat such disorders. Emphasis is placed on integrative and alternative treatments for such neurologic diseases as seizures, cerebrovascular accidents, canine cognitive disorder, meningitis, intervertebral disc disease, fibrocartilagenous embolism, degenerative myelopathy, and myopathies. Thorough physical and neurologic examinations, establishment of a correct diagnosis, and integrative therapeutics are aimed at improving the overall quality of life of the veterinary patient.     

Avian analgesia.

Understanding behavioral indicators of pain and other assessment techniques can help one to recognize pain in birds and prompt us to treat birds with analgesics. An analgesic plan needs to include several modalities to help reduce pain in the avian patient. Analgesic therapy should be directed at treating the disease/injury in the periphery, and the changes that occur in the central nervous system (CNS). Both opioid and nonsteroidal anti-inflammatory drug (NSAID) therapeutics can be selected to provide analgesia for the avian patient.     

Use of modified ciclosporin in the management of feline pemphigus foliaceus: a retrospective analysis

Background – Glucocorticoids as sole therapy for pemphigus foliaceus (PF) in cats are not always successful, and it is common to need additional immunomodulating agents to manage the disease. Hypothesis/Objectives – This retrospective study evaluated the use of modified ciclosporin as an adjuvant or sole immunomodulating drug in cats with PF and compared their response to PF cats managed with chlorambucil. Animals – Fifteen client‐owned cats diagnosed with PF that received ciclosporin and/or chlorambucil as part of their treatment and had adequate follow‐up to assess treatment response were evaluated. Methods – Records were reviewed from feline PF patients presented between the years of 1999 and 2009. Cats were divided into two treatment groups: those treated with ciclosporin and those treated with chlorambucil. Most cats in both groups also received concurrent systemic glucocorticoids. Each group contained six patients. Three cats were treated with both medications and are discussed separately. Time to disease remission, remission‐inducing glucocorticoid dose, maintenance or final glucocorticoid dose, disease response and adverse effects were assessed. Results – There was no significant difference in remission times or disease response between groups. All six patients maintained with ciclosporin for PF management were weaned off systemic glucocorticoids, while glucocorticoid therapy was stopped in only one of the six cats receiving chlorambucil. Conclusions and clinical importance – Modified ciclosporin is effective in the management of feline pemphigus foliaceus and is glucocorticoid sparing.     

Cytokine therapy: a natural alternative for disease control

Disease control in food production animals is normally mediated through the use of vaccines, chemicals and antibiotics. However, the extensive use of antibiotics and chemicals in livestock has resulted in environmental and human health concerns, particularly with regard to the emergence of drug-resistant bacteria in the food chain. In fact, the World Health Organisation (WHO) has now urged meat producers to use environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators of the immune response, offer exciting alternatives to conventional therapeutics. The utilisation of cytokines is becoming more feasible with the recent cloning of a number of cytokine genes. Since the chicken's immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review our recent studies on the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter.     

Diabetes mellitus induced in a dog after administration of corticosteroids and methylprednisolone pulse therapy

An 8-year-old ovariohysterectomized Chow Chow was referred because of dermatologic lesions diagnosed as pemphigus foliaceus. Intolerance to orally administered corticosteroids necessitated the use of methylprednisolone pulse therapy. One week after treatment, diabetes mellitus was diagnosed on the basis of blood and urine test results. For 3 years after treatment, the dog has remained a well-regulated diabetic. Complete remission of pemphigus foliaceus is maintained by alternate-day, orally administered prednisone (0.5 mg/kg of body weight).     

Structural and functional basis for the long QT syndrome: relevance to veterinary patients

Long QT syndrome (LQTS) is a condition characterized by prolongation of ventricular repolarization and is manifested clinically by lengthening of the QT interval on the surface ECG. Whereas inherited forms of LQTS associated with mutations in the genes that encode ion channel proteins are identified only in humans, the acquired form of LQTS occurs in humans and companion animal species. Often, acquired LQTS is associated with drug-induced block of the cardiac K+ current designated I(Kr). However, not all drugs that induce potentially fatal ventricular arrhythmias antagonize I(Kr), and not all drugs that block I(Kr), are associated with ventricular arrhythmias. In clinical practice, the extent of QT interval prolongation and risk of ventricular arrhythmia associated with antagonism of I(Kr) are modulated by pharmacokinetic and pharmacodynamic variables. Veterinarians can influence some of the potential risk factors (eg, drug dosage, route of drug administration, presence or absence of concurrent drug therapy, and patient electrolyte status) but not all (eg, patient gender/genetic background). Veterinarians need to be aware of the potential for acquired LQTS during therapy with drugs identified as blockers of HERG channels and I(Kr).     

Immunologic diseases

Selected equine cutaneous diseases for which there is strong evidence of an immunological aetiology are discussed in this section. The reactive disorders of urticaria, Culicoides hypersensitivity, erythema multiforme, drug eruptions and systemic granulomatous disease are included. The autoimmune diseases of the horse with cutaneous manifestations (pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and cutaneous lupus erythematosus) are discussed. The clinical signs and diagnostic features of these immunologically induced equine dermatoses are defined, and the challenges in making a definitive diagnosis and managing the clinical signs are confirmed.     

A review of autoimmune skin diseases in domestic animals: I - superficial pemphigus

In humans, the pemphigus denomination encompasses a group of autoimmune blistering skin diseases with intraepidermal separation resulting from cell-cell detachment by acantholysis. Entities are classified based on the level of blistering in the epidermis, and both superficial (pemphigus foliaceus, IgA pemphigus) and deep (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) variants are recognized. In domestic animals, subsets of pemphigus have been recognized since the mid-1970s, and the disease classification resembles that used for human patients. This article reviews up-to-date knowledge on the epidemiology, clinical signs, histopathology, immunopathology and treatment outcome of superficial pemphigus in domestic animals. Detailed information on canine, feline, equine and caprine pemphigus foliaceus, canine and feline pemphigus erythematosus and canine panepidermal pustular pemphigus is provided.     

Comparative analysis of canine dermatophytosis and superficial pemphigus for the prevalence of dermatophytes and acantholytic keratinocytes: a histopathological and clinical retrospective study

Acantholytic dermatophytosis is a rarely reported condition of dogs that clinically and histopathologically mimics superficial pemphigus (erythematosus, foliaceus). Histologically, periodic acid-Schiff (PAS) and Grocott's methenamine-silver (GMS) are often necessary to show the fungus. A retrospective histopathological study was conducted on 190 canine skin biopsy specimens: 95 each with the diagnosis of canine dermatophytosis or of superficial pemphigus. All specimens were stained with haematoxylin and eosin, PAS, and GMS. Dermatophytes were not seen in any superficial pemphigus cases. Acantholytic keratinocytes were noted in 14% of the dermatophytosis cases, none of which had clinical signs consistent with superficial pemphigus. Among cases with acantholytic keratinocytes, superficial pemphigus had significantly more acantholytic cells than dermatophytosis (P = 0.02). When comparing face and nonface cases, there was no difference in prevalence of acantholytic keratinocytes in dermatophytosis or number of acantholytic keratinocytes in superficial pemphigus. All dermatophyte cases were both GMS and PAS positive with neither stain being visually superior. No dermatophyte cases where acantholytic keratinocytes were noted had a history, clinical signs and histopathological features compatible with acantholytic dermatophytosis.     

Practical considerations in emergency drug therapy.

Drug therapy is integral to emergency and critical care medicine but can also be the source of serious medical errors. There are important considerations with regard to drug, route, and interactions that require close attention in critical patients. The continuous development of new therapeutics and new information concerning current therapies requires practitioners to continually review drug therapies. This article addresses general guidelines, routes of administration, dosage calculations, interactions, monitoring recommendations, and resources available to help clinicians improve their drug therapy practices.     

Counter current line absorption immunoelectrophoresis in an alternative diagnostic screening test to counter current immunoelectrophoresis in Aleutian disease (AD) eradication programs

Counter current immunoelectrophoresis (CCIE) is the diagnostic method used in the ongoing Aleutian disease virus eradication program on Danish mink farms. There has been an increasing demand for an alternative diagnostic test especially to evaluate suspected false positive CCIE reactions. We compared test results of a number of negative and positive mink sera in indirect counter current immunoelectrophoresis (ICCIE), counter current line absorption immunoelectrophoresis (CCLAIE) and radio immuno assay (RIA) with test results from counter current immunoelectrophoresis and found that counter current line absorption immunoelectrophoresis is the best alternative diagnostic screening test to counter current immunoelectrophoresis for Aleutian disease eradication programs. Not only proved the CCLAIE test to be useful for evaluation of doubtfully positive CCIE reactions, but it was found to have a higher sensitivity than the CCIE test.     

Diagnosis and medical treatment of otitis externa in dogs and cats

A review of otitis externa in dogs and cats is presented. Aetiology, includes primary causes: ectoparasitoses, allergic diseases, endocrine disorders, pyodermas, trauma and irritation, contact dermatitis, auto-immune skin diseases, drug eruption, keratoseborrhoeic skin disease, tumours and pseudoneoplastic lesions, as well as secondary causes: bacteria and yeasts. Clinical aspects are variable but a practical classification distinguishes two forms: erythematoceruminous otitis externa and suppurative otitis externa. Diagnosis is made in five steps which are clinical examination, direct examination of cerumen (erythematoceruminous otitis externa) or bacterial culture and sensitivity testing (suppurative otitis externa), direct impression smears, cleaning and otoscopy, and diagnosis of underlying skin disease. Medical therapy includes cleaning of the external ear canal and local therapy (acaricides, antifungal agents, antibiotics, corticosteroids, other topical agents, the appropriate selection of an optic preparation being essential). Treatment of underlying skin disease is always necessary. Otitis externa is in fact a dermatological disease complex (like pododermatitis). Although local secondary infections (bacterial and fungal) must be managed in every case, there are grounds for including otitis externa in a larger frame.     

The emerging role of avian cytokines as immunotherapeutics and vaccine adjuvants

The use of antibiotic feed additives and chemical antimicrobials in food production animals is a double-edged sword. On one hand, it helps to prevent the outbreak of disease and promotes the growth of animals, but on the other hand, concerns are mounting over the emergence of antibiotic-resistant bacteria. As a consequence, some countries have already banned the use of in-feed antibiotics which has resulted in meat producers urgently seeking environmentally friendly alternative methods to control disease. Cytokines are proteins that control the type and extent of an immune response following infection or vaccination. They therefore represent excellent naturally occurring therapeutics. The use of cytokines in poultry has become more feasible with the discovery of a number of avian cytokine genes. Since the immune system of chickens is similar to that of mammals, they offer an attractive model system to study the effectiveness of cytokine therapy in the control of disease in livestock. This review will focus on the recent advances made in avian cytokines, with a particular focus on their assessment as therapeutic agents and vaccine adjuvants.     

Localization of immunoglobulins and complement by the peroxidase antiperoxidase method in autoimmune and non-autoimmune canine dermatopathies

Formalin-fixed, paraffin embedded skin biopsy specimens from 44 dogs with various dermatopathies were examined for the presence of immunoglobulins (IgG, IgM, IgA) and complement (C3) by the peroxidase antiperoxidase method (PAP). Final diagnoses of the skin diseases were determined by clinical findings, fungal and bacterial cultures, skin scrapings, serum endocrinologic tests, and histologic features of cutaneous biopsies. The dermatopathies included examples of pyoderma (folliculitis/furunculosis), demodecosis, sarcoptic mange, dermatophytosis, endocrine dermatopathy, and autoimmune skin disease (AISD). In the latter category, 7 cases of pemphigus foliaceus, 1 pemphigus vulgaris, 4 discoid lupus erythematosus (DLE) and 4 examples of indeterminate AISD were examined. Immunoglobulins, C3, or both, were localized in tissue sections from AISD (15/16), pyoderma (7/11), demodecosis (4/8) sarcoptic mange (3/3), and dermatomycosis (2/3). Endocrine dermatopathy biopsies were consistently negative for Ig and C3 (0/3). The pattern of localization was most often intercellular (31/44 positive biopsies) with basement membrane immunoreactivity in 4 cases of DLE, and 1 case of indeterminate AISD. There was no consistent correlation between histologic features of hematoxylin and eosin-stained biopsies and the presence of Ig and C3. Clinical outcome was similar in both Ig and C3 positive and negative cases of non-AISD dermatitis. The high percentage (95%) of positive results in AISD biopsies indicates the usefulness and sensitivity of the PAP method for the localization of Ig and C3. Because of the high percentage of Ig localization in pyoderma (73%), biopsy specimens with extensive inflammatory skin disease are not suitable for diagnosis of AISD. The PAP method is useful in the diagnosis of AISD in biopsy specimens with minimal inflammation. Caution is warranted in the interpretation of immunoreactivity independent of clinical and histologic information.     

Subepidermal linear alignment of mast cells in inflammatory dermatoses of the dog

A recent study demonstrated that 47.7% of dogs with Malassezia dermatitis had a subepidermal linear alignment of mast cells (SLAM). A retrospective histopathological study was conducted on 419 canine skin biopsies to determine if a SLAM was present in other inflammatory diseases. Cases examined included dogs with demodicosis, sarcoptic mange, dermatophytosis, pemphigus foliaceus, pemphigus erythematosus, discoid lupus erythematosus, systemic lupus erythematosus, erythema multiforme, dermatomyositis, staphylococcal pyoderma, primary seborrhea, arthropod bites, contact hypersensitivity, flea bite hypersensitivity, atopy, and food hypersensitivity. Three cases (3/419, 0.7%) were identified with SLAM. The diagnoses for these cases were atopy (1/23, 4%) with a secondary bacterial folliculitis (1/136, 0.7%), pemphigus erythematosus (1/18, 6%), and discoid lupus erythematosus (1/16, 6%). Based on this study, SLAM is significantly more common in Malassezia dermatitis than in other inflammatory diseases.