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.

SOAT1 missense variant in two cats with sebaceous gland dysplasia.

Spontaneously arisen hereditary diseases in domestic animals provide an excellent opportunity to study the physiological functions of the altered genes. We investigated two 4-month-old sibling domestic short haired kittens with dry dark debris around the eyes, nose, and ears, dark crusting on the legs and a thin poor hair coat. Skin biopsies revealed abnormal sebaceous gland morphology with lack of normal sebocyte arrangement and differentiation. Hair follicles had a distorted silhouette, interpreted as a change secondary to the observed sebaceous gland dysplasia. Whole genome sequencing on both affected kittens and 65 genetically diverse feline genomes was performed. Filtering for variants that were present in both kittens but absent from the control genomes revealed a homozygous missense variant in SOAT1, encoding sterol O-acyltransferase 1. The protein is localized in the endoplasmic reticulum and catalyzes the formation of cholesteryl esters, an essential component of sebum and meibum. The identified SOAT1:c.1531G > A variant is predicted to change a highly conserved glycine residue within the last transmembrane domain of SOAT1, p.Gly511Arg. In mice, variants in Soat1 or complete knockout of the gene lead to the "hair interior defect" (hid) or abnormal Meibomian glands, respectively. SOAT1:c.1531G > A represents a plausible candidate variant for the observed sebaceous gland dysplasia in both kittens of this study. The variant was not present in 10 additional cats with a similar clinical and histopathological phenotype suggesting genetic heterogeneity. SOAT1 variants should be considered as potential cause in hereditary sebaceous gland dysplasias of humans and domestic animals.

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.

Abnormal sebaceous gland differentiation in 10 kittens ('sebaceous gland dysplasia') associated with generalized hypotrichosis and scaling.

A rare congenital dermatosis, characterized by progressive hypotrichosis with variable scaling and crusting, occurred in 10 short-haired kittens in North America and Europe. Lesions appeared at between 4 and 12 weeks of age, commencing on the head and becoming generalized. The tail was spared in two kittens. Generalized scaling was mild to moderate, often with prominent follicular casts. Periocular, perioral, pinnal and ear canal crusting was occasionally severe. The skin was thick and wrinkled in two kittens. Histologically, the main lesion was abnormal sebaceous gland morphology. Instead of regular differentiation from basal cells to mature sebocytes, the glands were composed of a haphazard collection of undifferentiated basaloid cells, some partly vacuolated and a few containing eosinophilic globules. Mitotic figures and apoptotic cells were present in an irregularly thickened follicular isthmus. Lymphocytic mural folliculitis and mild sebaceous adenitis were rare. Orthokeratotic hyperkeratosis and follicular casts were present. Hair follicles were of normal density and were mostly in anagen, but some contained malacic hair shafts. Perforating folliculitis, leading to dermal trichogranuloma formation, occurred occasionally. Further biopsy samples taken at 2 years and at 3 and 4 years, respectively, from two kittens revealed similar but often more severe sebaceous gland lesions. Hair follicles were smaller, with many in telogen. The young age of onset suggests a genetic defect interfering with sebaceous and, possibly, follicular development. These lesions are discussed with reference to studies of mouse mutants in which genetic defects in sebaceous differentiation cause a similar phenotype of hyperkeratosis and progressive alopecia.

A report of 7 cases of feline vulval adenocarcinoma.

Seven cases of feline vulval adenocarcinoma are reported. Follow-up information was available for 5 cats, and all but 1 of these was euthanized within 2-18 mo of diagnosis (median 9.2 mo) for reoccurrence of local disease (3 cases) and/or clinical signs consistent with metastases (3 cases). There was no relationship between histological features of the tumor and outcome.

Bacillary angiomatosis in an immunosuppressed dog.

A dog being treated with immunosuppressive doses of prednisone and azathioprine for pancytopenia of unknown origin, developed, over a 2-week period, multiple erythematous nodular lesions in the skin including footpads. Skin samples revealed lesions identical to those of human bacillary angiomatosis (BA). The nodules were composed of multifocal proliferations of capillaries, each lined by protuberant endothelial cells. The capillary clusters were separated by an oedematous connective tissue, lightly infiltrated with degenerate inflammatory cells, including neutrophils and macrophages. Tissue sections stained with Warthin-Starry silver stain revealed large numbers of positively stained bacilli in the stromal tissue, most heavily concentrated around the proliferating capillaries. Lesions of vascular degeneration and inflammation were evident. Bartonella vinsonii subsp. berkhoffii genotype 1 was independently amplified and sequenced from the blood and the skin tissue. The pathognomonic nature of the histological lesions, demonstration of compatible silver-stained bacilli in the tissue, and identification of B. vinsonii subsp. berkhoffii in the blood and tissue indicates that this is most likely the aetiologic agent responsible for the lesions. Antibiotic therapy was successful in resolving the nodules. It would appear that B. vinsonii subsp berkhoffii, like Bartonella henselae and Bartonella quintana, has the rare ability to induce angioproliferative lesions, most likely in association with immunosuppression. The demonstration of lesions identical to those of human BA in this dog is further evidence that the full range of clinical manifestations of human Bartonella infection occurs also in canines.

Induction of delayed-type hypersensitivity and interferon-gamma to Candida albicans and anti-hen-egg white lysozyme antibody as phenotypic markers of enhanced bovine immune response.

Delayed-type hypersensitivity (DTH) is a protective localized cell-mediated immune response (CMIR), primarily against intracellular pathogens. DTH is widely used in research to assess immune responsiveness and has been a valuable diagnostic test in commercial settings. In pigs and other species both antibody (AMIR) and CMIR have been considered as reliable phenotypic markers of selection programs for disease resistance. Therefore in cattle, it was also considered important to find antigen/adjuvant combinations capable of inducing AMIR and CMIR without interfering with diagnostic tests. The objectives of the present study were to evaluate the combined use of hen-egg white lysozyme (HEWL) and Candida albicans adjuvanted with Quil A in lactacting Holstein cows for the induction of anti-HEWL antibody, as well as DTH and IFN-gamma to C. albicans as phenotypic markers of enhanced immune responsiveness. Thirty one lactating Holstein cows were immunized with HEWL to induce antibody responses and C. albicans to sensitize for DTH. Two test antigens, candin and C. albicans whole cell (CaWC), were used to induce the effector phase of DTH. PBS was used as the negative control. In addition, two different skin sites (neck versus tail) were tested to evaluate differences in skin site responsiveness. C. albicans-induced IFN-gamma production, as an indicator of a type 1 response, was evaluated by ELISA. Microscopic evaluation of skin samples at DTH sites was performed in five randomly selected cows and these skin biopsies were scored based on inflammation and cell infiltration. Results demonstrated the presence of classical DTH response to C. albicans, in that DTH responses peaked at 24 h post-intradermal injections and cell infiltration was composed largely of mononuclear leukocytes, typical of DTH skin reactions in cattle. The only difference in test antigens was that DTH to candin showed a higher early response (6 h) than CaWC and a rapid decrease in inflammation from 24 to 48 h. The neck was significantly more sensitive than the tail skin-fold as a DTH test site. IFN-gamma was detected on days 14 and 21 post-immunization in plasma from blood incubated with candin. Significant primary and secondary anti-HEWL antibodies were also detected, indicating that this combination of test antigens could be used as phenotypic markers of immune responsiveness in cattle.

Raccoonpox in a Canadian cat.

Poxvirus infections affecting the skin of cats are extremely rare in North America, in contrast to Europe where cowpox virus is well recognized as an accidental pathogen in cats that hunt small rodents. The virus or viruses responsible for the anecdotal cases in North America have never been characterized. This paper reports a case of raccoonpox infection in a Canadian cat. Biopsy of the initial ulcerative lesion on the forepaw revealed ballooning degeneration of surface and follicular keratinoctyes. Infected cells contained large eosinophilic type A inclusions. Electron microscopic examination revealed virions of an orthopoxvirus, subsequently identified as raccoonpox by polymerase chain reaction and gene sequencing. The cat made a full recovery.

Extratesticular interstitial and Sertoli cell tumors in previously neutered dogs and cats: a report of 17 cases.

Primary neoplasms derived from testicular tissue and in an extratesticular location are extremely rare. Clinical and surgical information was collected and verified from 15 different submitting practices for 12 dogs and 5 cats that spontaneously developed neoplasms of testicular origin after castration. Eleven dogs had Sertoli cell tumors in an extratesticular location. One dog and all 5 cats had an extratesticular interstitial cell tumor. Six animals (1 dog, 5 cats) had developed secondary sexual characteristics that reversed after removal of the tumor. All had a palpable mass in the scrotum or at the site of the original prescrotal incision. No animals died of neoplasia-related disease and no metastases were identified. Several possibilities, including the presence of embryological ectopic tissue or the presence of testicular tissue transplanted during castration, are considered as causal.

Underlying medical conditions in cats with presumptive psychogenic alopecia.

OBJECTIVE: To identify underlying medical conditions in cats with a presumptive diagnosis of psychogenic alopecia. DESIGN: Case series. ANIMALS: 21 adult cats referred with a presumptive diagnosis of psychogenic alopecia. PROCEDURES: A detailed behavior and dermatologic questionnaire was completed by the primary caregiver, and complete behavioral and dermatologic examinations were performed. A standard diagnostic testing protocol that included cytologic examination of skin scrapings, fungal culture of hairs, evaluation of responses to parasiticides and an exclusion diet, assessment for atopy and endocrinopathies, and histologic examination of skin biopsy specimens was used to establish a definitive diagnosis in all cats. Cats that did not respond to an elimination diet were treated with methylprednisolone acetate to determine whether pruritus was a factor. RESULTS: Medical causes of pruritus were identified in 16 (76%) cats. Only 2 (10%) cats were found to have only psychogenic alopecia, and an additional 3 (14%) cats had a combination of psychogenic alopecia and a medical cause of pruritus. An adverse food reaction was diagnosed in 12 (57%) cats and was suspected in an additional 2. All cats with histologic evidence of inflammation in skin biopsy specimens were determined to have a medical condition, but of 6 cats without histologic abnormalities, 4 had an adverse food reaction, atopy, or a combination of the 2, and only 2 had psychogenic alopecia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that psychogenic alopecia is overdiagnosed in cats. Thorough diagnostic testing should be done before ascribing a behavioral cause to hair loss in cats.

Evaluation of bovine cutaneous delayed-type hypersensitivity (DTH) to various test antigens and a mitogen using several adjuvants.

The Bacillus Calmette Guerin (BCG)-induced/purified protein derivative (PPD)-elicited tuberculin skin test is a reliable measure of cell-mediated immune response (CMIR), specifically delayed-type hypersensitivity (DTH); however, its use in livestock may confound diagnosis of Mycobacterium tuberculosis. Therefore, various alternative antigen/adjuvant combinations were evaluated as inducers of DTH that were compared to the BCG/PPD test system with the purpose of finding a skin DTH protocol that does not cross-react with the tuberculin test and allows identification of high and low CMIR responder phenotypes. Specifically, 30 non-lactating cows (five/treatment) were sensitized on day 0 with mycobacteria [BCG, M. tuberculosis or Mycobacterium phlei cell wall extract (MCWE)], and ovalbumin (OVA) emulsified in Freund's complete adjuvant (FCA), non-ulcerative Freund's adjuvant (NUFA), complete NUFA or MCWE. On day 21, cows were injected intradermally with various test antigens including PPD tuberculin, phlein, and OVA. Phosphate buffered saline was included as the negative control and the T-cell mitogen phytohemagglutinin (PHA) was also administered. Double skin-fold thickness was evaluated before and at 6, 24, and 48 h post-injection. Skin biopsies were taken at 24 and 48 h to assess oedema, necrosis, and inflammatory cell infiltration. BCG/PPD and M. phlei/phlein treatments when given with a Freund's adjuvant induced equivalent DTH with peak reactions at 24-48 h after antigen injection. Cows receiving NUFA had fewer injection site granulomas than FCA or CNUFA treatments. The change in skin thickness response to PHA peaked at 6 h. Only cows receiving mycobacteria in NUFA had skin response to OVA, which peaked 6-24 h post-injection. Only sites tested with PPD or phlein had significantly higher lymphocyte infiltration than control, whereas neutrophils were significantly higher at PHA test sites and eosinophils predominated at the PHA test sites. Macrophages were significantly more numerous at the PPD and/or phlein test sites in treatment groups that received killed mycobacteria in a Freund's adjuvant and/or with BCG, and at the PHA test sites in all treatment groups. It was concluded that the M. phlei/phlein system did induce DTH and was similar to the DTH induced by the BCG/PPD system when MCWE was administered with a Freund's adjuvant. Therefore, this protocol is suitable for detecting high/low CMIR responders in research herds. However, cross-reaction to PPD was evident following induction of DTH using M. phlei. Hence, this protocol does not alleviate the problem of artificial induction of DTH cross-reactivity and would not be suitable for commercial herds where tuberculin testing is required.

Graft-versus-host disease in severe combined immunodeficiency/beige mice administered canine leukocytes.

This report describes the development and lesions of graft-versus-host disease (GVHD) in severe combined immunodeficiency/ beige (SCID/BG) mice after the administration of canine leukocytes. Intraperitoneal injections of 0.87 x 10(7) canine lymphocytes were given to each of 9 mice; 5 mice received no canine lymphocytes. Morphologic evidence of successful engraftment included peritoneal aggregates of lymphocytes and repopulation of spleen and lymph nodes by lymphocytes. Canine CD45R was expressed by 2.25% of peripheral blood leukocytes in the 1 mouse tested 65 d after engraftment but by none of the cells of a control mouse. Canine immunoglobulin G was detected in serum samples from 5 of the 6 tested mice given canine lymphocytes but none of the control mice. By 13 to 65 d after receiving canine lymphocytes, 5 of the 9 mice had died of GVHD or had been euthanized because of it; all the control mice remained healthy. Lesions of GVHD included hemolytic anemia, cholangiohepatitis, alveolitis, and disseminated intravascular coagulation. Serum from the donor dog and from all 15 randomly selected dogs caused agglutination of normal mouse erythrocytes, supporting a diagnosis of immune-mediated hemolytic anemia in the dog-mouse chimeras. All of the mouse serum tested contained murine immunoglobulin, and this "leakiness" may have contributed to the development of GVHD.

Characterization of a potential animal model of an idiosyncratic drug reaction: nevirapine-induced skin rash in the rat.

Idiosyncratic drug reactions are difficult to study in humans due to their unpredictability. Unfortunately, this characteristic also hinders the development of animal models needed for mechanistic studies. Nevirapine, used to treat human immunodeficiency virus (HIV) infections, results in a severe idiosyncratic skin rash in some patients. We found that nevirapine can also cause a significant rash in some strains of rats. At a dose of 150 mg/kg/day, the incidence in female Sprague-Dawley rats was 6/28 (21%), in female Brown Norway rats 32/32 (100%), and in female Lewis rats 0/6 (0%) while no male Sprague-Dawley or Brown Norway rats developed a rash. Female SJL mice 0/7 also did not develop nevirapine-induced skin lesions. The first sign of a reaction in Brown Norway rats was red ears at days 7-10 followed by a rash with scabbing mainly on the back; this was a shorter time to onset than in Sprague-Dawley rats. Light microscopy of the skin revealed a primarily mononuclear inflammatory infiltrate and lesions typical of self-trauma. Immunohistochemistry results suggest that the infiltrate was composed of CD4 and CD8 T cells as well as macrophages. A lower dose of either 40 or 75 mg/kg/day did not lead to a rash and, in fact, 2 weeks of the lower doses induced tolerance to the 150 mg/kg/day dose in female Brown Norway rats. A dose of 100 mg/kg/day resulted in rash in 2/4 (50%) of female Brown Norway rats. Rechallenge of Brown Norway rats that had been allowed to recuperate after a nevirapine-induced rash led to red ears in less than 24 h followed by hair loss and occasional skin lesions. Although the skin rash was less evident on rechallenge, microscopically, the cellular infiltrate was more prominent, especially surrounding the hair follicles. Moreover, there were lesions of interface dermatitis with apoptosis and satellitosis, indicative of a cell-mediated immune attack on the epidermis. While systemic signs of illness did not accompany the rash on primary exposure, on rechallenge, the animals appeared generally unwell and this forced sacrifice after 2 weeks or less of treatment. Importantly, splenocytes isolated from rechallenged animals were able to transfer susceptibility to nevirapine-induced skin rash to naïve female Brown Norway recipients, which was illustrated by a faster time to onset of rash in the recipients. The characteristics of this adverse reaction are similar to that seen in humans; that is, it is idiosyncratic in that it only occurs in some strains of animals, is delayed in onset, is more common in females, is dose-dependent, and appears to be immune-mediated. Therefore, it may represent a good animal model for the study of idiosyncratic drug reactions.

A retrospective study of 44 canine apocrine sweat gland adenocarcinomas.

Apocrine sweat gland adenocarcinomas (AACs) are relatively uncommon skin tumors in dogs. Little prognostic or behavioral information has been published for these tumors. In this retrospective study, 44 AACs from diagnostic archives were reexamined and clinical postexcisional follow-ups for 25 of the 44 cases were obtained by a survey. There were 28 out of 44 (65.9%) AACs that invaded the capsule, stroma, or both, 5 of 44 (11.4%) invaded blood vessels and stroma, and 1 out of 25 (4%) had distant metastases. The presence or absence of stromal and vascular invasion was predicted by clinical examination with more than 80% accuracy. Postexcisional median survival of dogs with AACs was 30 mo at the time of survey. Determination of a correlation between histological features and malignant behavior of AACs was compromised by the low number of cases with clinical AAC-related problems; however, it appears that intravascular invasion is an important indicator of potential systemic metastases.

Detection of papillomavirus-DNA in mesenchymal tumour cells and not in the hyperplastic epithelium of feline sarcoids.

We examined 12 formalin-fixed paraffin-embedded feline skin tumours which had the histopathological features of fibropapillomas for the presence of papillomavirus (PV) DNA using touchdown polymerase chain reaction (PCR), DNA sequencing and nonradioactive in situ hybridization. Nine of the tumours contained a 102-bp PCR product demonstrated using consensus PV primers that amplify a portion of the L1 gene. The nucleotide sequences are closely related, but not identical to that of ovine PV type 2, rabbit oral PV and reindeer PV. The deduced amino acid sequences had strong homologies with the major capsid protein L1 of deer PV, bovine papillomavirus (BPV) 1 and BPV 2, and European elk PV. Although PV antigens were not detected in any of the tumours by immunohistochemistry, PV DNA was demonstrated in individual mesenchymal cells or cell nests of 4/12 tumours by in situ hybridization. A nonproductive infection of mesenchymal fibroblast-like tumour cells with a papillomavirus would explain the lack of PV antigen expression and the absence of PV DNA in the hyperplastic epithelium. Because these tumours and their pathogenesis are similar to equine sarcoids, we suggest that they should be reclassified as 'feline sarcoids' instead of fibropapillomas.

Résumé Nous avons examiné 12 blocs parrafinés de tumeurs cutanées du chat ressemblant à des fibropapillomes afin de rechercher par PCR, séquençage de l'ADN et hybridisation non radioactive in situ la presence de papillomavirus (PV). Neuf tumeurs présentaient un produit de PCR 102 bp, mis en evidence par un primère PV qui amplifie une portion du gène L1. Les séquences nucléotidiques étaient proches, mais non identiques au PV ovin de type 2, au PV oral du lapin, et au PV du renne. Les séquences d'acides aminés avaient des homologies marquées avec la protéine de la capside L1 du cerf, du papillomavirus bovin de type 1 et 2. Alors que les techniques immunohistochimiques n'ont pas permis de mettre en évidence d'antigènes de PV, de l'ADN de PV a été retrouvé dans les cellules mésenchymateuses ou les cordons cellulaires de 4/12 tumeurs par hybridisation in situ. Une infection non productive des cellules tumorales mésenchymateuses fibroblastiques par un papillomavirus pourrait expliquer l'absence d'expression d'antigènes de PV et l'absence d'ADN de PV dans l'épithélium hyperplasique. Comme ces tumeurs sont semblables aux sarcoïdes équins, nous suggérons qu'elles soient reclassées comme des 'sarcoïdes félins' plutôt que comme des fibropapillomes.

Resumen Examinamos 12 tumores cutáneos felinos, fijados en formalina e incluidos en parafina, con características histopatológicas de fibropapiloma, para determinar la presencia de DNA de papilomavirus (PV) utilizando una 'touchdown' PCR, secuenciación del DNA e hibridación in situ no radioactiva. Nueve de los tumores contenían un producto de la PCR de 102 pb, obtenido con cebadores consensuales ('consensos primers') de PV que amplifican una porción del gen L1. Las secuencias de nucleótidos están íntimamente relacionadas, pero no son idénticas al PV ovino tipo 2, PV oral del conejo o al PV del caribú. Las secuencias de aminoácidos deducidas tenían fuertes homologías con la proteína de la capside mayor L1 del PV del ciervo, PV bovino (PVB) 1 y el PVB 2, y PV del ciervo europeo. Mientras que los antígenos del PV no fueron detectados immunoquímicamente en ninguno de los tumores, ADN PV fue demostrado, mediante hibridación in situ, en células mesenquimatosas individuales o en grupos de células en 4/12 tumores. Una infección no productiva con un papilomavirus de las células fibroblásticas mesenquimatosas explicaría la falta de expresión de antígenos PV y la ausencia de DNA PV en el epitelio hiperplásico. Debido a que estos tumores y su patogénesis son similares a los sarcoides equinos, sugerimos que deberían clasificarse como 'sarcoides felinos' en lugar de fibropapilomas.

Adoptive transfer of BALb/c mouse splenocytes reduces lesion severity and induces intestinal pathophysiologic changes in the Mycobacterium avium Subspecies paratuberculosis beige/scid mouse model.

Successful immune reconstitution would enhance resistance of beige/scid mice to chronic infection with Mycobacterium avium subspecies paratuberculosis, but may cause damage to intestinal tissue. Therefore, we investigated the effect of adoptive transfer of BALB/c mouse splenocytes on lesion severity and intestinal physiology in beige/scid mice infected with M. paratuberculosis. Mice were inoculated intraperitoneally (i.p.) with M. paratuberculosis, and two weeks later were inoculated i.p. with viable spleen cells from immune-competent BALB/c mice. Mice were necropsied 12 weeks after infection when engraftment of lymphocytes, clinical disease, pathologic lesions, and intestinal electrophysiologic parameters were evaluated. Lymphocytes were rare in control beige/scid mice not inoculated with spleen cells. In contrast, high numbers of CD4+, CD8+, and B220+ lymphocytes were detected in the spleen of all beige/scid mice (n = 24) inoculated with spleen cells, indicating that adoptive transfer resulted in successful engraftment of donor lymphocytes (immune reconstitution). Immune reconstitution of M. paratuberculosis-infected beige/ scid mice significantly reduced the severity of clinical disease and pathologic lesions, and numbers of bacteria in the liver. However, intestinal electrophysiologic parameters studied in vitro indicated that intestinal tissues from reconstituted beige/scid mice had reduced short-circuit current responses (due to reduced ion secretion) following electrical, glucose, and forskolin stimulation. These abnormal responses suggested that neural or epithelial cells in the intestine were damaged. We conclude that successful immune reconstitution of beige/scid mice enhance their resistance to M. paratuberculosis infection, but may cause pathophysiologic changes associated with intestinal inflammation.

Resident Dendritic Cells in the Epidermis: Langerhans Cells, Merkel Cells and Melanocytes.

Résumé- En plus des kératinocytes, l'épiderme contient des cellules résidentes de morphologie dendritique. Ce sont principalement la cellule de Langerhans, la cellule de Merkel et le mélanocyte. Ces cellules ont des fonctions diverses dans le tégument. Le mélanocyte assure la pigmentation cutanée et la protection contre les radiations U.V., et pourrait intervenir également dans la modulation de l'inflammation cutanée. La cellule de Langerhans intervient dans la surveillance immunologique des surfaces corporelles ecternes. La cellule de Merkel a des fonctions neuroendocrines. Cet article donne un aperçu de la structure et de la fonction de ces trois importantes populations cellulaires dans la peau. [Resident dentritic cells in the epidermis: Langerhans cells, Merkel cells and melanocytes (Cellules dentritiques résidentes de l'épiderme: cellules de Langerhans, cellules de Merkel et mélanocytes). Resumen- La epidermis contiene, además de los queratinocitos, células résidentes de morfologia dendria dendritica. Estas son principalmente las células de Langerhans, las células de Merkel y los melanocitos. Estas células tienen varias funciones en el integumento. Los melanocitos se encargan de la pigmentación y protección de la piel contra la radiación ultravioleta y tarrtbién participan en la regulación de la inflamación cutánea. Las células de Langerhans ayudan en la regulación inmunológica en la superficie externa. Las células de Merkel tienen funciones neuroendocrinas. Esta revisión da un repaso general a la estructura y función de tres importantes células de la piel. [Resident dendsuitic cells in the epidermis: Langerhans cells, Merkel cells and Melanocytes (Células résidentes en la epidermis: células de Langerhans, células de Merkel y melanocitos). Abstract- In addition to the keratinocytes, the epidermis contains resident cells of dendritic morphology. These are principally the Langerhans cell, Merkel cell and melanocyte. These cells have a number of different functions in the integument. The melanocyte is responsible for skin pigmentation and protection against UV radiation, and may also play a role in the modulation of cutaneous inflammation. The Langerhans cell aids in the immunological monitoring of the body's external surfaces. The Merkel cell has neuroendocrine functions. This review gives an overview of the structure and function of these three important cells of the skin.

Canine Demodicosis: A Re-examination of the Histopathologic Lesions and Description of the Immunophenotype of Infiltrating Cells.

Résumé- Cette étude décrit les modelités réactionnelles inflammatoires et l'immunophénotype des lésions histologiques de démodécie canine. Trois modalités principales sont décrites: une folliculite pariétale, une folliculite suppurative et furonculose, et une dermatite modulaire. La folliculite pariétale, réaction inflammatoire ciblée sur la paroi folliculaire, est présente dans tous les cas et constitue la modalité réactionnelle principale dans 17 cas sur 34 (50 pour cent). Le sous-type interface, caractérisé par une dégénérescence hydropique ou une apoptose des kératinocytes folliculaires, avec exocytose lymphocytaire, s'observe dans 15 de ces 17 cas. Une mélanose folliculaire et/ou une incontinence pigmentaire sont présentes sur 10 de ces 17 biopsies. Une dermatite nodulaire, représentée par un granulome périfolliculaire, est présente sur neur biopsies (26 pour cent). Une folliculite suppurative ou une furonculose est la modalité relationnelle dominante dans huit cas (24 pour cent). Tous les lymphocytes dans la paroi folliculaire sont des lymphocytes T CD3+, contre 10 pour cent sculement des cellules périfolluculaires. Les plasmocytes IgG+ constituent jusqu'à 74 pour cent des cellules périfolliculaires, et le pourcentage est encore plus élevé dans les cas de furonculose. Ces faits montrent que la folliculite pariétale est une lésion importante dans la démodécie canine, et suggère qu'une réaction à médiation cellulaire est dirigée spécifiquement contre la paroi folliculaire. [Canine demodicosis: a re-examination of the histopathologic lesions and description of the immunophenotype of infiltrating cells (La démodécie canine: réexamen des lésions histologiques et description de l'inmunophénotype des cellules infiltrantes). Resumen- Este estudio describe los patrones inflamatorios y el immunofenotipo de las lesiones histológicas en la demodicosis canina. Se identificaron tres patrones principales: foliculitis mural, foliculitis y furunculosis supurative, y dermatitis nodular. La foliculitis mural, una reacción inflatatoria dirigida a la pared folicular, se observó en todos los casos y constituia el patrón principal en 17 de los 34 casos (50%). En 15 de estos 17 casos la foliculitis mural era de tipo interfase, caracterizada por degeneración hidrópica o apoptosis de queratinocitos foliculares y exocitosis linfocitica. Se detectó melanosis folicular y/o incontinecia pigmentaria en 10 de estas 17 biopsias. Neuve biopsias (26 por ciento) presentaban dermatitis nodular, caracterizada por granulomas perifoliculares. Ocho casos (24 por ciento) mostraban foliculitis o furunculosis como patrón dominante. Linfocitos T CD3+ constituian la totalidad del infiltrado en la pared folicular, mientras que el mismo tipo celular representaban el 10 por ciento del infiltrado inflamatorio perifolicular. Hasta el 74 por ciento de las células perifoliculares eran células plasmáticas IgG+, con el mayor número en casos con furunculosis. Estos hallaz os indican que la foliculitis mural es una lesion importante la demodicosis canina y sugiere que una reacción mediada por células es dirigida a la pared folicular. [Canine demodicosis: a re-examination of the histopathological lesions and description of the immunophenotype of infiltrating cells (Demodicosis canina: repaso de las lesiones histopatológicas y descripción del inmunofenotipo del infiltrado celular). Abstract- This study describes the inflammatory patterns and immunophenotype of the histologic lesions of canine demodicosis. Three major patterns were identified: mural folliculitis, suppurative folliculitis and furunculosis and nodular dermatitis. Mural folliculitis, an inflammatory reaction targeting the follicular wall, was seen in all cases and was the principle pattern in 17 of 34 cases (50 per cent). The interface subtype of mural folliculitis, typified by hydropic degeneration or apoptosis of follicular keratinocytes and lymphocytic exocytosis, occurred in 15 of these 17 cases. Follicular melanosis and/or pigmentary incontinence occurred in 10 of these 17 biopsies. Nodular dermatitis, represented by perifollicular granulomas, was present in nine biopsies (26 per cent). Suppurative folliculitis or furunculosis was the dominant pattern in eight cases (24 per cent). All lymphocytes within the follicular wall were CD3+ T lymphocytes, compared to 10 per cent of the perifollicular cells. IgG+ plasma cells accounted for up to 74 per cent of perifollicular cells, highest in cases with furunculosis. These findings indicate that mural folliculitis is an important lesion of canine demodicosis, and suggests that a cell-mediated reaction is targeting the follicular wall.