ETV6 represses inflammatory response genes and regulates HSPC function during stress hematopoiesis in mice.

ETS variant 6 (ETV6) encodes a transcriptional repressor expressed in hematopoietic stem and progenitor cells (HSPCs), where it is required for adult hematopoiesis. Heterozygous pathogenic germline ETV6 variants are associated with thrombocytopenia 5 (T5), a poorly understood genetic condition resulting in thrombocytopenia and predisposition to hematologic malignancies. To elucidate how germline ETV6 variants affect HSPCs and contribute to disease, we generated a mouse model harboring an Etv6R355X loss-of-function variant, equivalent to the T5-associated variant ETV6R359X. Under homeostatic conditions, all HSPC subpopulations are present in the bone marrow (BM) of Etv6R355X/+ mice; however, these animals display shifts in the proportions and/or numbers of progenitor subtypes. To examine whether the Etv6R355X/+ mutation affects HSPC function, we performed serial competitive transplantation and observed that Etv6R355X/+ lineage-sca1+cKit+ (LSK) cells exhibit impaired reconstitution, with near complete failure to repopulate irradiated recipients by the tertiary transplant. Mechanistic studies incorporating cleavage under target and release under nuclease assay, assay for transposase accessible chromatin sequencing, and high-throughput chromosome conformation capture identify ETV6 binding at inflammatory gene loci, including multiple genes within the tumor necrosis factor (TNF) signaling pathway in ETV6-sufficient mouse and human HSPCs. Furthermore, single-cell RNA sequencing of BM cells isolated after transplantation reveals upregulation of inflammatory genes in Etv6R355X/+ progenitors when compared to Etv6+/+ counterparts. Corroborating these findings, Etv6R355X/+ HSPCs produce significantly more TNF than Etv6+/+ cells post-transplantation. We conclude that ETV6 is required to repress inflammatory gene expression in HSPCs under conditions of hematopoietic stress, and this mechanism may be critical to sustain HSPC function.

Regional alopecia and dermatitis due to Lodderomyces elongisporus in a North American porcupine (Erethizon dorsatum).

BACKGROUND: Lodderomyces elongisporus is a yeast with a worldwide distribution that has been reported as a cause of infection in immunocompromised humans and in a dog that had been quilled by a porcupine. OBJECTIVES: The objective of this report is to describe the clinical presentation, diagnosis and treatment of dermatitis caused by L. elongisporus in a North American porcupine (Erethizon dorsatum). ANIMAL: One wild adult male North American porcupine from New York state, USA. METHODS AND MATERIALS: The porcupine was presented for alopecia and scaling dermatitis over the caudal dorsum. Diagnostic testing included cytological evaluation, trichogram, bacterial and fungal culture, and histopathological examination of skin biopsies. RESULTS: Histopathological findings from skin specimens demonstrated mild eosinophilic perivascular-to-interstitial dermatitis with superficial dermal fibrosis, mild epidermal hyperplasia with moderate-to-marked intracorneal and intrafollicular yeast. Fungal culture with matrix-assisted laser desorption/ionization confirmed L. elongisporus as the cause of the dermatitis. The porcupine was treated with a six week course of oral itraconazole with clinical resolution. CLINICAL RELEVANCE: Infection with L. elongisporus should be included as a differential diagnosis for North American porcupines exhibiting signs of dermatitis including scaling and alopecia. This case report may be relevant for the diagnosis and treatment of porcupines with dermatitis and for animals or humans that have been quilled by a porcupine.

Looking back on 45 years of canine dermatology.

In June 2018, I was honored (and flabbergasted!) to receive the Kennel Club Charitable Trust's Lifetime Achievement Award for research in the field of canine health, sponsored by Vernon and Shirley Hill of Metro Bank, and administered by the Kennel Club Charitable Trust. I entered the arena of veterinary dermatology in 1971, a graduate of the University of California, Davis. I retired from Cornell University as the James Law Professor Dermatology Emeritus in 2016. During my 45-year career in veterinary dermatology, I worked with all species, especially dogs, cats, and horses, eventually authoring or co-authoring 694 publications including 12 textbooks. For this personal view I will limit my comments to canine dermatology. I was asked to make this article 'a more reflective piece on my lifetime's work'. This is not at all comfortable for me, as my upbringing encouraged me not to 'toot my own horn'. However, 'toot' I must. Hence, indulge me as I share these very personal views on where we were, where we went, and some of my own dabblings along the way. If I fail to mention one of your favorite remembrances, I apologize. Don't let it get under your skin!

Resident lymphocytes in the dermis of the normal dorsolateral thoracic skin of alpacas.

BACKGROUND: Small numbers of resident T lymphocytes are present in the dermis of normal skin of humans, cattle and sheep. HYPOTHESIS/OBJECTIVES: We wanted to determine the prevalence, numbers and immunophenotype of lymphocytes in the dermis of healthy skin from alpacas. ANIMALS: Skin biopsy specimens were collected from the dorsolateral thorax of 31 alpacas with normal skin. METHODS: Skin biopsy specimens were evaluated for the prevalence and numbers of CD3+ and CD79a+ lymphocytes. RESULTS: Resident CD3+ and CD79a+ lymphocytes were found around the superficial and deep dermal blood vessels. The CD3+ lymphocytes were more numerous than CD79a+ lymphocytes. Both CD3+ and CD79a+ lymphocytes were more numerous around superficial dermal blood vessels. CONCLUSIONS AND CLINICAL IMPORTANCE: Resident CD3+ and CD79a+ lymphocytes are present around superficial and deep dermal blood vessels in normal skin from alpacas; hence, the presence of lymphocytes in these locations without obvious features of inflammation must be interpreted cautiously when evaluating skin biopsy specimens from alpacas with skin disease.

Scaling dermatosis in three dogs associated with abnormal sebaceous gland differentiation.

BACKGROUND: Abnormal sebaceous gland differentiation, so-called 'sebaceous gland dysplasia', is a rare condition described in the dog and the cat. Although little is known about this condition, it is thought that a genetic defect causes abnormal sebaceous gland development. Clinically, this condition occurs in young cats and dogs and is characterized by variable degrees of adherent scale, hair casts, poor coat quality and hypotrichosis. HYPOTHESIS/OBJECTIVE: Here, we describe the clinical presentation and treatment of three adult dogs with abnormal sebaceous gland differentiation. ANIMALS: Three adult dogs presented with a keratinization defect characterized by progressive scaling, hair casts, dull, dry, brittle hair coat and hypotrichosis beginning in puppyhood to early adulthood. METHODS: Multiple 6 mm punch skin biopsy samples were obtained from each dog. Treatments included various topical keratomodulatory agents, oral essential fatty acids and oral vitamin A. RESULTS: Histologically, all sebaceous glands were small and composed of a mixture of irregularly clustered basal reserve cells and mature sebocytes. With therapy, two of the dogs showed moderate to marked clinical improvement in scaling, hair casts and hair coat quality. CONCLUSIONS AND CLINICAL IMPORTANCE: Although rare, 'sebaceous gland dysplasia' should be considered in cases where a primary keratinization defect is suspected. Given that abnormal sebaceous differentiation is a structural defect of the skin, treatment must be maintained and is aimed at ameliorating the clinical signs rather than curing the disease.

Resident lymphocytes in the epidermis and adnexal epithelia of normal dorsolateral thorax of alpacas.

A small population of resident T-lymphocytes is present in the normal epidermis of skin from humans, mice, sheep, and cattle. The objective of this study was to determine the prevalence of lymphocytes, CD3+ cells (T-lymphocytes) and CD79a+ cells (B-lymphocytes and plasma cells), in the epidermis and adnexal epithelia of alpacas. Skin-biopsy specimens from the normal skin of the dorsolateral thorax of 31 alpacas were examined histologically and immunohistochemically for the presence of CD3+ cells and CD79a+ cells in the epidermis and adnexal epithelia. CD3+ T-lymphocytes, but not CD79a+ cells, were present in the epidermis and adnexal epithelia. Therefore, in the absence of other signs of inflammation, the presence of lymphocytes in these structures in skin-biopsy specimens should be considered normal.

Une petite population de lymphocytes T résidents est présente dans l'épiderme normal de la peau des humains, des souris, des moutons et des bovins. L'objectif de la présente étude était de déterminer la prévalence des lymphocytes, des cellules CD3+ (lymphocytes T) et cellules CD79a+ (lymphocytes B et cellules plasmatiques), dans l'épiderme et l'épithélium annexiel des alpagas. Des spécimens de biopsie cutanée provenant de la peau normale du thorax dorso-latéral de 31 alpagas ont été examinés en histopathologie et par immunohistochimie pour la présence de cellules CD3+ et CD79a+ dans l'épiderme et l'épithélium annexiel. Des lymphocytes T CD3+, mais pas des cellules CD79a+, étaient présentes dans l'épiderme et l'épithélium annexiel. Ainsi, en absence d'autres signes d'inflammation, la présence de lymphocytes dans ces structures dans des spécimens de biopsies cutanées devrait être considérée comme étant normale.(Traduit par Docteur Serge Messier).

Feline dermatology at Cornell University: 1407 cases (1988-2003).

Medical records of 1407 cats with dermatologic diagnoses made at Cornell University teaching hospital from 1988 to 2003 were tabulated. We expressed the diagnoses as counts, percentages of the cats with dermatologic disease (1407) and percentages of all cats seen at the university hospital (22,135) during the same period. A total of 1887 diagnoses were made in the 1407 cats. We compared the age, sex and breed group of our cases with all those 22,135 cats in ('1-by-c') χ(2) tests in which the hospital population was considered a standard (rather than a 'sample'). The 10 most common dermatoses, their counts, and the proportions of dermatologic diagnoses and of the total cat population that the cats with these dermatoses represented were: allergy (298; 15.8%; 1.35%), atopic dermatitis (194; 10.3%; 0.88%), bacterial folliculitis/furunculosis (189; 10.0%; 0.85%), otodectic mange (115; 6.1%; 0.52%), flea infestation (99; 5.2%; 0.45%), feline acne (74; 3.9%; 0.33%), flea-bite allergy (70; 3.7%; 0.32%), cutaneous adverse drug reaction (56; 3.0%; 0.25%), idiopathic eosinophilic-granuloma complex (55; 2.9%; 0.25%) and abscess (51; 2.7%; 0.23%). Allergies of all types, combined, accounted for 32.7% of all the feline dermatoses. Relative to the standard of the total hospital population, cats <2 years old and females (both intact and spayed) were significantly under-represented (all P≤0.001) in the dermatologic case series. In contrast, Himalayans (compared with domestic short- or longhair, Persian, Siamese and other breeds) and males (both intact and neutered) were significantly over-represented (all P ≤0.001).

An open clinical trial on the efficacy of cetirizine hydrochloride in the management of allergic pruritus in cats.

Cetirizine hydrochloride was administered orally at 5 mg/cat, q24h, to 32 cats with allergic skin disease. Pruritus was reduced in 41% (13/32) of the cats. The antipruritic effect was repeatable and sustainable. There was no significant association between patient age, disease severity, or cutaneous reaction pattern and improvement during cetirizine administration. No adverse side effects were reported.

Alopecia areata in two black Angus cows.

Adult onset progressive alopecia and leukotrichia developed in 2 registered black Angus cows, aged 6 and 7 years. Histopathologic findings in skin were prominent melanin clumping and degeneration of matrix cells with formation of giant multinucleate cells within hair bulbs, accompanied by peribulbar melanin incontinence and fibrosis and dystrophic hair shafts. Intrabulbar and peribulbar lymphocytes were cluster of differentiation (CD)3-positive T cells. Findings were characteristic of alopecia areata.

Skin diseases in the alpaca (Vicugna pacos): a literature review and retrospective analysis of 68 cases (Cornell University 1997-2006).

This retrospective study describes 68 alpacas with skin diseases investigated from 1997 through 2006 at Cornell University. During this time period, 40 of 715 (5.6%) alpacas presented to the university hospital had dermatological diseases. In addition, skin-biopsy specimens accounted for 86 of 353 (24.4%) of alpaca biopsy specimens submitted to the diagnostic laboratory, and of these 86 specimens, follow-up was available for 28 cases. The following diseases were most common: bacterial infections (22%); neoplasms, cysts and hamartomas (19%); presumed immunological disorders (12%); and ectoparasitisms (10%). Conditions described for the first time included intertrigo, collagen and hair follicle hamartomas, lymphoma, hybrid follicular cysts, melanocytoma, anagen defluxion, telogen defluxion, presumed insect-bite hypersensitivity, ichthyosis, and possible hereditary bilateral aural haematomas and chondritis. The results of the retrospective study are compared and contrasted with the results of a literature review.

The microanatomy of healthy skin from alpacas (Vicugna pacos).

The microanatomy of healthy skin from 12 different body sites was investigated in 14 alpacas (Vicugna pacos). The microanatomy of alpaca skin is typical of domestic animal skin in general, and closely resembles that from llamas.

CD3+ and BLA.36+ cells do not occur in the epidermis and adnexal epithelia of normal skin from the dorsolateral trunk of cats.

A small population of resident T-lymphocytes is present in the normal epidermis of humans, mice, and rats. However, resident epidermal lymphocytes have not been reported in the normal skin of the cat. Skin-biopsy specimens from the normal skin of the dorsolateral trunk from 30 cats were examined histologically and immunohistochemically for the presence of lymphocytes, CD3+ cells, and BLA.36+ cells in epidermis and adnexal epithelia. All examinations were negative. It appears that lymphocytes occur rarely, if at all, in the epidermis and adnexal epithelial of normal cat skin. Hence, the presence of lymphocytes in these structures should be considered abnormal.

Prevalence of apoptotic epidermal keratinocytes in eosinophilic dermatoses of the cat: a retrospective light-microscopic study of 145 skin-biopsy specimens.

A retrospective light-microscopic study was performed on skin-biopsy specimens from 145 cats with eosinophilic inflammatory dermatoses in order to determine the prevalence of apoptotic epidermal keratinocytes (AKs), the prevalence of eosinophils in close proximity to AKs, and whether there was a difference in the prevalence of AKs or the prevalence of eosinophils in close proximity to AKs based on histopathological reaction pattern. Overall, 62/145 (43%) specimens had AKs. Of the cases in which AKs were seen, 18% had eosinophils in close proximity to the AKs. The specimens were divided into three groups based on histopathological reaction pattern: perivascular-to-interstitial, diffuse, and nodular. No difference in the prevalence of AKs was found among the three histological groups. Because the sample size containing eosinophils in close proximity to AKs was too small to compare the three histological patterns individually, nodular and non-nodular patterns were compared. No difference in the presence of eosinophils in close proximity to AKs was found in these two subsets. More AKs were present if eosinophils were in close proximity to the AKs (range 1-9 with eosinophils near compared to 0-7 without).