A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy

Acute systemic toxoplasmosis was diagnosed in a 4-5-year-old, male, Domestic Short Hair cat, which had been on cyclosporine A immunomodulatory therapy for feline atopy, over an 8-month period. Cyclosporin A (CsA) has shown promising results as a immunosuppressive agent in the cat for the treatment of eosinophilic plaque and granulomas, allergic cervico-facial pruritus, feline atopy and other immune-mediated dermatoses. However, inhibition of T-lymphocyte function by CsA is believed to have predisposed this cat to the development of a newly acquired, acute Toxoplasma gondii infection, as characterized by severe hepatic and pancreatic pathology in conjunction with the heavy parasite load demonstrated on immunohistochemical (IHC) stains for T. gondii. Cats on CsA therapy appear to be at risk of developing fatal systemic toxoplasmosis.     

Non-pruritic granuloma in Norwegian forest cats

The eosinophilic granuloma complex is a group of skin disorders common in cats. This paper describes the clinical, haematological and histopathological features of 17 related Norwegian forest cats, six of which had a linear granuloma on the caudal thigh, three of which also had a granuloma on the lower lip, and one of which had a granuloma in combination with an indolent ulcer. The high prevalence of the disease in this population is suggestive of a genetic background.     

Prospective open pilot study on the use of ciclosporin for feline allergic skin disease

OBJECTIVES: To evaluate the efficacy of ciclosporin in cats with allergic skin disease. METHODS: Ten cats with signs of allergic skin disease were administered ciclosporin daily at a dose of 3.6 to 8.3 mg/kg for one month. None of these cats had previously responded to a hypoallergenic diet trial, and all animals had previously been treated with endectoparasiticidal drugs, with no improvement two weeks before entering the trial. On days 0 and 30, owners assessed pruritus with a visual analogue scale, and veterinarians evaluated cutaneous lesions. RESULTS: All the cats had pruritus and erythema, five had alopecia, two had an eosinophilic plaque, one had miliary dermatitis and two had both alopecia and an eosinophilic plaque. Good or excellent improvement was observed in 40 per cent of cats for pruritus, 57 per cent of cats for alopecia and 60 per cent of cats for erythema. A significant decrease in mean scores was observed for pruritus only, while for erythema and alopecia, it was close to being significant (P < 0.052). CLINICAL SIGNIFICANCE: Ciclosporin may be helpful in symptomatically treating signs of feline allergic skin disease. However, it is important to remember that ciclosporin is not licensed for use in cats.     

Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study

In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate–potassium clavulanate (Clavamox^®; Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin‐clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase‐positive staphylococci were the most commonly isolated bacteria. The amoxicillin‐clavulanate‐treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (?7.60 cm², P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), whereas the placebo group did not. The amoxicillin‐clavulanate‐treated lip ulcer group had a 42.6% decrease in mean lesion size (?0.25 cm², P = 0.4125) and the placebo group a 36.6% increase (+0.49 cm², P = 0.1575), although neither change was statistically significant. The amoxicillin‐clavulanate‐treated lip ulcer group had a statistically significant 65.0% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), while no significant reduction was observed in the placebo group. A suspension of amoxicillin trihydrate–potassium clavulanate is an effective monotherapy for the treatment of feline eosinophilic plaques.     

Feline herpesvirus 1-associated facial and nasal dermatitis and stomatitis in domestic cats.

Feline herpesvirus-associated dermatitis has rarely been reported. Recently we documented a unique ulcerative and often persistent facial dermatitis or stomatitis syndrome associated with feline herpesvirus 1. We believe this syndrome is relatively common, with the 10 cases in our series diagnosed between 1996 and 1997. The syndrome is associated with epithelial cell necrosis, eosinophilic inflammation, and intraepithelial herpesvirus inclusion bodies. The prevalence of eosinophilic inflammation and low number of inclusion bodies may lead to the misdiagnosis of allergic dermatitis or a lesion within the eosinophilic granuloma complex group of disorders. Feline herpesvirus 1 can be identified in lesional tissue by PCR methodology. Most of our cases developed under circumstances suggesting reactivation of latent herpesvirus infection, and previous glucocorticoid therapy or stress from overcrowding may have played a role in lesion development. Cats with ulcerative dermatitis, especially of the face and nose, and cats with stomatitis should be evaluated for the presence of feline herpesvirus. Treatment options include surgical excision, topical or systemic antibiotic therapy to treat secondary bacterial infection, and oral alpha interferon.     

The efficacy of cyclosporine A in cats with presumed atopic dermatitis: a double blind, randomised prednisolone-controlled study

The objective of this study was to compare the efficacy of cyclosporine A (CsA) and prednisolone in feline atopic dermatitis (AD) in a randomised, controlled double blind study. Twenty-nine cats with feline AD were randomly allocated to two groups. Eleven cats were treated orally with prednisolone (1mg/kg SID) and 18 were treated with CsA (5mg/kg/day) for 4 weeks. At day 0 (D0) and D28, skin lesions were graded by means of the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies and intradermal allergy tests were performed at D0 and blood samples for haematology and serum biochemistry were collected at D0 and D28. During the trial the cat owners were asked to evaluate the intensity of the pruritus once weekly on a linear analog scale and to record side effects. Based on the CADESI there was no significant difference between the two groups in the amount of remission (P=0.0562) or in the number of cats that improved by >25% (P=0.0571). The effect of CsA and prednisolone on pruritus as evaluated by the owners was not significantly different (P=0.41) between the two groups. No serious side effects were observed. The conclusion was that CsA is an effective alternative to prednisolone therapy in cats with presumed atopic dermatitis.     

Ulcerative facial and nasal dermatitis and stomatitis in cats associated with feline herpesvirus 1

Ulcerative dermatitis of the nasal planum or haired skin of the face, associated with intranuclear inclusion bodies compatible with herpesvirus, was identified in nine cats. Clinically, lesions were ulcerative and crusted, and often persistent. A tenth cat had focal proliferative ulcerative stomatitis, also associated with intranuclear inclusion bodies. Microscopically, there was necrosis and ulceration associated with prominent eosinophilic inflammation. Intranuclear inclusion bodies were noted in all cases, within the surface or adnexal epithelium. Ultrastructural examination of skin from two cats revealed virions morphologically compatible with a herpesvirus. Polymerase chain reaction (PCR) specific for feline herpesvirus 1 on DNA extracted from fresh-frozen or formalin-fixed paraffin-embedded biopsy samples and/or consensus primer PCR with DNA sequencing performed on DNA extracted from formalin-fixed paraffin-embedded biopsy samples from seven cats revealed that the virus was indistinguishable from feline herpesvirus 1. PCR was negative in one of eight cats tested.     

Cyclosporine A inhibits transcription of cytokine genes and decreases the frequencies of IL-2 producing cells in feline mononuclear cells

Cyclosporine A (CsA) has been widely used for suppression of transplant rejection and controlling pruritus in allergic dermatitis in humans, dogs and cats. CsA is known to suppress the expression of inflammatory cytokines, including IL-2, IL-4, IFN-gamma and TNF-alpha in humans, dogs and experimental mice. However, little is known about the immunomodulating effect of CsA in cats. The aim of this study was to evaluate the effects of CsA on the expression of inflammatory cytokines in feline peripheral blood mononuclear cells (PBMC). Real-time PCR analyses with Concanavalin A (ConA)-stimulated PBMC obtained from 5 cats revealed that the expression of mRNAs for IL-2, IL-4, IFN- gamma and TNF-alpha was inhibited by CsA in a dose-dependent manner. Moreover, an enzyme-linked immunospot (ELISPOT) assay, which is capable of detecting IL-2 secreting cells as single spots, revealed that the frequency of IL-2 secreting cells in ConA-stimulated feline PBMC was significantly reduced in the presence of CsA. These results might provide an explanation for the mechanisms of action of CsA in the suppression of transplant rejection and the control of pruritus in cats.     

Quantitative analysis of tryptase- and chymase-containing mast cells in eosinophilic conditions of cats

The presence and density of tryptase-positive/chymase-positive mast cells (MCs) (MC(TC)), chymase-positive/tryptase-negative MCs (MCC), and tryptase-positive/chymase-negative MCs (MC(T)) in lesional skin from cats with eosinophilic conditions were investigated. Skin biopsy specimens from eight cats with eosinophilic plaque (three cats), eosinophilic granuloma (two cats), and eosinophilic dermatitis (three cats) were studied. Toluidine blue staining and a double-enzyme-immunohistochemical staining technique were performed to determine MC density and MC subtypes, respectively. MC density varied from 170.3 to 503 cells/mm2 (mean value of 314.9 cells/mm2). In the superficial dermis, 5.9% of the MC belonged to the MC(T), 12.8% to the MC(C), and 81.2% to the MC(TC) subtype. In the deep dermis, 12.8% belonged to the MC(T), 12.8% to the MC(C), and 73.8% to the MC(TC) subtype. It is the first time that MC(C) have been identified. The double-labeling procedure proved to be a reliable tool for identifying simultaneously the presence of MC subtypes in feline skin.     

Expression of RANTES mRNA in skin lesions of feline eosinophilic plaque

Abstract One of the mechanisms of eosinophil infiltration is its induction by chemoattractants such as regulated upon activation, normal T-expressed and secreted (RANTES) which is a cysteine–cysteine chemokine that mediates chemotaxis and activation of eosinophils in humans and mice. Skin lesions of feline eosinophilic plaque are characterized by a predominant infiltration of eosinophils. The mechanism(s) of eosinophilic infiltration in the skin and/or mucosa of cats is unknown. It is possible that RANTES is involved. To investigate the presence of RANTES in the skin of cats with eosinophilic plaques and nonaffected skin, we cloned and sequenced the full-length feline RANTES cDNA gene, in order to determine whether it is present in the skin of cats with eosinophilic plaques and/or if it is present in normal adjacent skin. We were able to document the the expression of RANTES mRNAs in skin with feline eosinophilic plaque as well as in normal cat skin. The full-length cDNA sequence of the RANTES gene (742 bp) contained a single open reading frame of 276 bp encoding a protein of 92 amino acids. The amino acid sequence of feline RANTES shared 67 and 74% sequence identity with that of bovine and mouse RANTES genes, respectively. RT–PCR analysis on RANTES mRNA in the skin of cats with eosinophilic plaque revealed that its expression was higher in the eosinophilic plaque skin lesions than in the normal skin. The result suggested that RANTES might play a role to induce eosinophil infiltration in feline eosinophilic plaque lesions.     

Malassezia spp. overgrowth in allergic cats

A series of 18 allergic cats with multifocal Malassezia spp. overgrowth is reported: atopic dermatitis was diagnosed in 16, an adverse food reaction in another and one was euthanized 2 months after diagnosis of Malassezia overgrowth. All the cats were otherwise healthy and those tested (16 out of 18) for feline leukaemia or feline immunodeficiency virus infections were all negative. At dermatological examination, multifocal alopecia, erythema, crusting and greasy adherent brownish scales were variably distributed on all cats. Cytological examination revealed Malassezia spp. overgrowth with/without bacterial infection in facial skin (n = 11), ventral neck (n = 6), abdomen (n = 6), ear canal (n = 4), chin (n = 2), ear pinnae (n = 2), interdigital (n = 1) and claw folds skin (n = 1). Moreover, in two cats Malassezia pachydermatis was isolated in fungal cultures from lesional skin. Azoles therapy alone was prescribed in seven, azoles and antibacterial therapy in eight and azoles with both antibacterial and anti-inflammatory therapy in three of the cats. After 3-4 weeks of treatment, substantial reduction of pruritus and skin lesions was observed in all 11 cats treated with a combined therapy and in five of seven treated solely with azoles. Malassezia spp. overgrowth may represent a secondary cutaneous problem in allergic cats particularly in those presented for dermatological examination displaying greasy adherent brownish scales. The favourable response to treatment with antifungal treatments alone suggests that, as in dogs, Malassezia spp. may be partly responsible for both pruritus and cutaneous lesions in allergic cats.     

Interaction of clarithromycin with cyclosporine in cats: pharmacokinetic study and case report

Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough levels in human transplant patients. However, the interaction of CLM with CsA has not been reported in cats. In this study, the effects of oral dosing of CLM on the pharmacokinetics and dosing of CsA in cats were investigated. Co-administration of CLM with CsA resulted in significant increases of oral bioavailability of CsA. In addition, CLM reduced the CsA dosage required to maintain the therapeutic CsA trough levels to almost 35% of the initial CsA therapy and the dose frequency was successfully replaced from a twice a day schedule to once a day in a feline kidney transplant patient. The addition of CLM to the regular CsA-based immunosuppression could be used as an effective alternative to classical ketoconazole treatment in feline kidney transplant patients and may result in substantial cost saving and convenience for the cat owners.     

Responsiveness and validity of the SCORFAD, an extent and severity scale for feline hypersensitivity dermatitis

Background – Hypersensitivity (allergic) dermatitis (HD) is commonly seen in cats, causing pruritus and various patterns of skin lesions, including at least one of the following: head and neck excoriations, self‐induced alopecia, eosinophilic plaques and miliary dermatitis. Few studies have evaluated the efficacy of therapeutic interventions for feline HD, and although various scales have been considered, none has been formally validated for the assessment of disease severity and its response to therapy. Objective – To design and validate a novel scale (SCORing Feline Allergic Dermatitis; SCORFAD) to assess the value of different criteria used as outcome measures for the treatment of feline HD and to set minimal thresholds for defining the clinical success of tested interventions. Animals – One hundred client‐owned cats. Methods – The SCORFAD scale was designed to include the four most frequently identified lesion types in feline HD (eosinophilic plaque, head and neck excoriations, self‐induced alopecia and miliary dermatitis) across 10 body regions. The extent and severity of each lesion type were graded prior to inclusion and after 3 and 6 weeks in a clinical study to compare the efficacy of two doses of ciclosporin with placebo. Results – The SCORFAD scale was found to exhibit satisfactory content, construct, criterion and sensitivity to change. The percentage reduction in SCORFAD from baseline was determined to be the most valid assessment of clinical response. Inter‐ and intra‐observer reliability was not assessed. Conclusions and clinical importance – The SCORFAD scale is proposed for use as a validated tool for the assessment of disease severity and response to therapeutic interventions in clinical trials for feline HD.     

Serum allergen‐specific immunoglobulin E in atopic and healthy cats: comparison of a rapid screening immunoassay and complete‐panel analysis

Feline and canine atopic dermatitis are thought to have a similar immunopathogenesis. As with dogs, detection of allergen‐specific IgE in cat serum merely supports a diagnosis of feline atopy based on compatible history, clinical signs and elimination of other pruritic dermatoses. In this study, a rapid screening immunoassay (Allercept^® E‐Screen 2nd Generation; Heska AG, Fribourg, Switzerland; ES2G) was compared with a complete‐panel serum allergen‐specific IgE assay (Allercept^®; Heska AG; CP) in healthy cats with no history of skin disease and in atopic cats. The latter had no diagnosis of external parasitism, infection, food hypersensitivity or other skin disease explaining their pruritus, and expressed cutaneous reaction patterns typically associated with feline allergic skin disease (head, neck or pinnal pruritus, miliary dermatitis, self‐induced alopecia, eosinophilic granuloma complex). The proportion of cats positive on either the ES2G or the CP assays was not significantly different between the atopic and healthy cat groups. There was, however, strong agreement between the results of the ES2G and CP assay; overall, the two tests were in agreement for 43 of 49 (88%) serum samples. There was also strong agreement when individual allergen groups were evaluated (agreement noted: indoor, 41 of 49 samples; grasses/weeds, 37 of 49 samples; and trees, 41 of 49 samples). These results indicate that although neither test is diagnostic for feline atopic dermatitis, the screening assay is beneficial for predicting the results of a complete‐panel serum allergen‐specific IgE assay in cats.     

Clinical and histological evaluation of an analogue of palmitoylethanolamide, PLR 120 (comicronized Palmidrol INN) in cats with eosinophilic granuloma and eosinophilic plaque: a pilot study

Fifteen cats with eosinophilic granuloma or eosinophilic plaque were given PLR 120 at the dosage of 10 mg kg⁻¹ twice daily for one month. PLR-120 down-modulates mast cell degranulation via a receptor-mediated mechanism. No other drugs were permitted and cats were kept free of parasites throughout the study. A clinical evaluation and skin biopsies were performed before and after the treatment. Clinical improvement was assessed at 15 and 30 days. Mast cell numbers were counted and their granular content was assessed by densitometric analysis on toluidine blue-stained sections before and after the treatment. Ten of 15 (67%) cats showed clinical improvement of signs and lesions. There was no significant difference between mast cell numbers in skin biopsies taken before and after the trial, whereas the number of granules was significantly increased ( P < 0.009). This pilot study suggests that PLR-120 might be a useful drug for the treatment of eosinophilic granuloma and eosinophilic plaque.     

Ultrastructural study of cutaneous lesions in feline eosinophilic granuloma complex

The purpose of this study was to investigate the ultrastructural appearance of flame figures, reported to comprise a mixture of degenerate collagen and degranulated eosinophils, in feline eosinophilic granuloma complex (EGC). Skin specimens from eight cats with EGC and from two clinically healthy cats were examined by transmission electron microscopy. Flame figures appeared to comprise ultrastructurally normal collagen fibrils separated by oedema and surrounded by large numbers of degranulating eosinophils. Longitudinal sections of collagen fibrils displayed the characteristic cross-striation of normal dermal collagen. Feline eosinophils, analogous to human eosinophils, degranulated both by cytolysis and piecemeal degranulation. The results of this study suggest that flame figures form in feline EGC due to eosinophil recruitment and degranulation, and that collagen fibres are partially disrupted but collagen fibrils are not damaged. These findings suggest that eosinophil accumulation and the release of granule contents represent the primary events in feline EGC.     

Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex

A retrospective study of banked sera from 19 cats with the eosinophilic granuloma complex revealed that 68% of affected cats had circulating antibodies to components of normal cat epithelium. Seemingly, the eosinophilic granuloma complex of cats may be an autoimmune disease; however, epidermal damage caused by the eosinophilic granuloma complex may release altered self-antigens to which the cat's immune system responds.     

Mosquito bite-caused eosinophilic dermatitis in cats.

Eight cats had lesions on the nasal bridge, ears, and footpads, with histologic and hematologic features of a recently described seasonal form of eosinophilic granuloma complex. Four cats were examined in detail, and it was established that 2 of the 4 reacted to mosquito extract on intradermal skin testing read at 20 minutes. Neither of the 2 cats tested had deposits of immunoglobulins in lesional or perilesional skin. Lesions on all 4 cats resolved when kept at home behind insect screening, but flared up if the screening was removed. Mosquitoes that were observed to be biting and causing lesions were collected and identified. Other species of laboratory-reared mosquitoes were allowed to bite nonlesional skin of 1 affected cat, causing pruritus, erythematous crusting, and ulcerative lesions at the bite site, which was characterized histologically as eosinophilic dermatitis.     

Feline eosinophilic granuloma complex(ities): some clinical clarification

PRACTICAL RELEVANCE: The feline eosinophilic granuloma complex (EGC) comprises a group of clinically well recognised but poorly understood dermatoses that are common in cats. In many cases, lesions are severe and can be accompanied by varying degrees of (and sometimes considerable) pruritus and/or pain. In addition, lesions can be chronic and recurrent. It is, therefore, important to achieve a prompt and accurate diagnosis in order to provide optimal, often life-long, treatment for affected cats. PATIENT GROUP: There is no age predisposition or well documented breed predilection for the development of EGC lesions in cats. Some studies have reported a possible female predisposition, but this has not been consistently documented. CLINICAL CHALLENGES: The clinical diagnosis of EGC lesions is usually straightforward, but investigation of the potential underlying aetiology can pose a challenge for the clinician. Information on the indication for various diagnostic tests and their interpretation is lacking, and the tendency for these cases to be managed with chronic medical intervention prior to achieving a definitive diagnosis can further complicate the interpretation of any diagnostic investigation. In addition, successful therapeutic management of these cases can be challenging. Some cats suffer only a single episode of disease that resolves with treatment, while others have recurrent lesions and some of these can be refractory to treatment. The individual variation in both the clinical nature of the disease and the response to therapy could be related to disease severity, but could also be explained by differences in the underlying aetiopathogenesis. EVIDENCE BASE: This article reviews the published literature to discuss the complex aetiology of the EGC and present an overview of the different clinical presentations and diagnosis. A further and particular aim has been to provide some evidence-based recommendations for the management of this unusual group of dermatoses.     

Molecular cloning of the feline thymus and activation-regulated chemokine cDNA and its expression in lesional skin of cats with eosinophilic plaque

Thymus and activation-regulated chemokine (TARC) is a member of CC chemokine and plays an essential role in recruitment of CC chemokine receptor 4 positive Th2 cells to allergic lesion. To investigate the association of TARC in allergic inflammation of cats, a TARC cDNA was cloned from feline thymus by RT-PCR with 3' rapid amplification of cDNA ends (RACE) method. The feline TARC clone contained a full length open reading frame encoding 99 amino acids which shared 80.8%, 72.5%, 65.6% and 67.8% homology with dog, human, mouse and rat homologues, respectively. Expression of TARC mRNA was detected not only in thymus but also in spleen, lung, lymph node, kidney, small intestine, colon and skin of the normal cat tissues examined. Furthermore, it was found that TARC mRNA was strongly expressed in lesional skin of cats with eosinophilic plaque. The present results demonstrated that TARC might be involved in the pathogenesis of eosinophilic plaque in cats.