Pattern analysis for the diagnosis of inflammatory skin lesions in domestic animals: An overview.

Pattern analysis of inflammatory skin diseases is a technique that offers a systematic approach to the histologic diagnosis of skin diseases. First introduced to human dermatopathology in the 1970s, it was widely adopted by veterinary pathologists for the histologic diagnosis of skin diseases in animals. As the inflammatory pattern reflects, to varying extents, aspects of the underlying disease pathogenesis, its use has contributed to the recognition of novel skin diseases in domestic animals, particularly in dogs and cats. Alternative diagnostic approaches used in human dermatopathology, such as "tissue-reaction pattern" and a purely "anatomic approach" have not been as widely used in veterinary pathology. However, veterinary pathologists often combine pattern analysis with anatomic and etiologic factors. This overview outlines the technique, introduces the patterns, and discusses advantages and limitations of pattern analysis in veterinary diagnostic dermatopathology. While molecular analytic techniques and image informatics will undoubtedly prove to be revolutionary in many areas of diagnostic pathology, it is recognized in both human and veterinary arenas that the light microscopic interpretation of hematoxylin and eosin-stained tissue sections will remain the mainstay of routine dermatopathology diagnosis for the foreseeable future.

Nonthymoma-associated exfoliative dermatitis in 18 cats.

BACKGROUND: Exfoliative dermatitis has been described in cats as a paraneoplastic skin disease associated with thymoma. There are anecdotal reports of cases without thymoma, with various suspected aetiologies. HYPOTHESIS/OBJECTIVES: To identify common features, underlying causes, response to therapy and outcome of nonthymoma-associated exfoliative dermatitis in cats. METHODS: Retrospective analysis was carried out of cases presented to dermatology referral centres or cases submitted for histopathological examination. Detailed historical and clinical data were obtained and evaluated statistically. Histopathology was reviewed in a blinded fashion by three dermatopathologists, and PCR for herpesvirus was performed. RESULTS: Eighteen cats fulfilled all inclusion criteria. There was no sex, age or breed predisposition. All cats presented with severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely depressed. In all cats, thymoma was excluded radiographically and feline leukaemia virus tests were negative. Additional imaging procedures in 14 cats and postmortem examination in two cats did not detect neoplasia. Histopathology revealed interface dermatitis, mural interface folliculitis and sebaceous adenitis indistinguishable from findings in thymoma-associated cases. PCR for herpes DNA was negative. No aetiology was identified. Treatment in 12 cases consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one responded to antibiotics, one to shampoo, two went into spontaneous remission, and two did not receive any therapy and were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: Nonthymoma-associated exfoliative dermatitis in cats is clinically and histopathologically indistinguishable from thymoma-associated cases. Most cases benefit from immunosuppressive therapy; therefore, an immunopathological response to an undefined trigger is suspected.

Alopecia areata in Eringer cows.

Alopecia areata is a hair loss disorder in humans, dogs and horses with a suspected autoimmune aetiology targeting anagen hair follicles. Alopecia areata is only sporadically reported in cows. Recently, we observed several cases of suspected alopecia areata in Eringer cows. The aim of this study was to confirm the presumptive diagnosis of alopecia areata and to define the clinical phenotype and histopathological patterns, including characterization of the infiltrating inflammatory cells. Twenty Eringer cows with alopecia and 11 Eringer cows without skin problems were included in this study. Affected cows had either generalized or multifocal alopecia or hypotrichosis. The tail, forehead and distal extremities were usually spared. Punch biopsies were obtained from the centre and margin of alopecic lesions and normal haired skin. Histological examination revealed several alterations in anagen hair bulbs. These included peri- and intrabulbar lymphocytic infiltration, peribulbar fibrosis, degenerate matrix cells with clumped melanosomes and pigmentary incontinence. Mild lymphocytic infiltrative mural folliculitis was seen in the inferior segment and isthmus of the hair follicles. Hair shafts were often unpigmented and dysplastic. The large majority of infiltrating lymphocytes were CD3(+) T cells, whereas only occasional CD20(+) lymphocytes were present in the peribulbar infiltrate. Our findings confirm the diagnosis of T-cell-mediated alopecia areata in these cows. Alopecia areata appears to occur with increased frequency in the Eringer breed, but distinct predisposing factors could not be identified.

Linear organoid nevus in a dog.

A skin lesion classified as linear organoid nevus is reported in a female standard Schnauzer. The dog was brought to the clinic with multiple hyperpigmented, hyperkeratotic linear or ovoid plaques on the head, neck, trunk, ears, and limbs. Histological findings included severe orthokeratotic hyperkeratosis, focal parakeratosis and hyperplasia of both the epidermis and the follicular infundibular epithelium, and marked sebaceous hyperplasia. No improvement was noted with systemic retinoid therapy. This is the second linear organoid nevus described in a dog, and the first report of retinoid therapy for this disease.

Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.

Equine insect bite hypersensitivity (IBH) is a seasonally recurrent, pruritic skin disorder caused by an IgE-mediated reaction to salivary proteins of biting flies, predominantly of the genus Culicoides. The aim of this study was to define T cell subsets and cytokine profile in the skin of IBH-affected Icelandic horses with particular focus on the balance between T helper (Th) 1, Th2 and T regulatory (Treg) cells. Distribution and number of CD4+, CD8+ and Forkhead box P3 (FoxP3)+ T cells were characterized by immunohistochemical staining in lesional and non-lesional skin of moderately and severely IBH-affected horses (n=14) and in the skin of healthy control horses (n=10). Using real-time quantitative reverse transcription-polymerase chain reaction, mRNA expression levels of Th2 cytokines (Interleukin (IL)-4, IL-5, IL-13), Th1 cytokines (Interferon-γ), regulatory cytokines (Transforming Growth Factor ß1, IL-10) and the Treg transcription factor FoxP3 were measured in skin and blood samples. Furthermore, Culicoides nubeculosus specific serum IgE levels were assessed. Lesions of IBH-affected horses contained significantly higher numbers of CD4+ cells than skin of healthy control horses. Furthermore, the total number of T cells (CD4+ and CD8+) was significantly increased in lesional compared to non-lesional skin and there was a tendency (p=0.07) for higher numbers of CD4+ cells in lesional compared to non-lesional skin. While the number of FoxP3+ T cells did not differ significantly between the groups, the ratio of Foxp3 to CD4+ cells was significantly lower in lesions of severely IBH-affected horses than in moderately affected or control horses. Interestingly, differences in FoxP3 expression were more striking at the mRNA level. FoxP3 mRNA levels were significantly reduced in lesional skin, compared both to non-lesional and to healthy skin and were also significantly lower in non-lesional compared to healthy skin. Expression levels of IL-13, but not IL-4 or IL-5, were significantly elevated in lesional and non-lesional skin of IBH-affected horses. IL-10 levels were lower in lesional compared to non-lesional skin (p=0.06) and also lower (p=0.06) in the blood of IBH-affected than of healthy horses. No significant changes were observed regarding blood expression levels of Th1 and Th2 cytokines or FoxP3. Finally, IBH-affected horses had significantly higher Culicoides nubeculosus specific serum IgE levels than control horses. The presented data suggest that an imbalance between Th2 and Treg cells is a characteristic feature in IBH. Treatment strategies for IBH should thus aim at restoring the balance between Th2 and Treg cells.

Immunoglobulin E-bearing cells and mast cells in skin biopsies of horses with urticaria.

The pathogenesis of equine urticaria is not well understood. In man, urticaria has been associated with immunological and nonimmunological mechanisms leading to the release of various mediators by mast cells. Skin biopsies of 32 horses with a history of urticaria were stained with toluidine blue, a double-labelling method for chymase and tryptase, and immunohistochemistry for immunoglobulin (Ig)E. These horses were compared with horses with pemphigus foliaceus, insect bite hypersensitivity and control horses with healthy skin. Neither formalin fixation time nor biopsy site influenced the staining methods. No chymase-positive cells were found. In all groups of horses, cells staining with toluidine blue and for tryptase and IgE were found in the epidermis and hair follicle papilla and significantly more positively staining cells were observed in the subepidermal dermis compared with the deep dermis. Horses with urticaria had significantly more IgE-bearing cells in the subepidermal dermis than control horses. However, horses with urticaria had significantly fewer toluidine-blue-stained mast cells in both subepidermal and deep dermis compared with the insect bite hypersensitivity and pemphigus foliaceus groups. This study suggests that IgE-mediated reactions play a role in the pathogenesis of urticaria.