Publications by authors named "Didier Pin"

34 Publications

Extra-auricular lesions of proliferative and necrotizing otitis externa in three kittens.

Vet Dermatol 2021 May 7. Epub 2021 May 7.

Université de Lyon, VetAgro Sup, UP ICE, Marcy l'Etoile, F-69280, France.

Background: Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats with poorly understood pathogenesis. Extra-auricular (EA) lesions recently have been mentioned in a textbook and in one case report.

Objectives: To describe EA lesions associated with PNOE in three kittens.

Animals: A 6-month-old female domestic short hair (DSH) cat (Case 1), an 8-month-old female DSH cat (Case 2) and a 5-month-old female DSH cat (Case 3).

Methods And Results: All cases exhibited classical lesions of PNOE associated with EA lesions, generalised (cases 1 and 3) or limited to eyelids (Case 2). Lesions were characterised by thick, adherent, hyperkeratotic papules coalescing to plaques and attempts to remove the hyperkeratotic plaques resulted in erosions. Histopathological examinations revealed classical features of PNOE: severe acanthosis associated with a marked lymphocytic exocytosis, satellitosis and apoptotic keratinocytes at all levels of the epidermis and the outer root sheath of hair follicles. Cases 2 and 3 resolved spontaneously. Case 1 remained stable with topical tacrolimus and oral prednisolone after a short course of ciclosporin.

Conclusions And Clinical Importance: This report describes EA lesions of PNOE in three kittens. Such lesions may be underdiagnosed, and this report emphasises the role of a thorough clinical inspection in PNOE cases.
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http://dx.doi.org/10.1111/vde.12968DOI Listing
May 2021

Cutaneous and systemic granulomatous disease associated with hairy vetch toxicosis in a French Holstein dairy herd.

Vet Dermatol 2021 Apr 13;32(2):196-199. Epub 2021 Jan 13.

CHUVA pôle Animaux de Production, ENVA, Maisons-Alfort, 94700, France.

This report describes an outbreak of hairy vetch toxicosis afflicting a herd of cattle with a fatal cutaneous and systemic granulomatous disease. It highlights how this condition remains poorly recognized by cattle production professionals in Europe and the need for communication about vetch-associated diseases.
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http://dx.doi.org/10.1111/vde.12927DOI Listing
April 2021

A moisturizer formulated with glycerol and propylene glycol accelerates the recovery of skin barrier function after experimental disruption in dogs.

Vet Dermatol 2020 Oct 6;31(5):344-e89. Epub 2020 Jul 6.

VetAgro Sup, UP ICE, Université de Lyon, 69280, Marcy l'Étoile, France.

Background: Moisturizers are foundational therapies for human atopic dermatitis. In veterinary medicine, the use of moisturizers has been recommended by an expert committee to alleviate skin dryness that would occur, for example, in canine atopic dermatitis (cAD). However, little is known regarding the effects of moisturizers on the skin barrier.

Hypothesis/objectives: To investigate the effects of a moisturizer on skin barrier recovery in a canine model of chronic mechanical barrier disruption.

Animals: Six healthy beagle dogs maintained in a laboratory setting.

Methods And Materials: A model of chronic skin barrier disruption was simulated by tape stripping on both sides of the thorax. The moisturizer then was applied twice daily for one week to one side of the thorax, while the other hemithorax was left untreated. The effects were evaluated by measurement of transepidermal water loss (TEWL) at various times during skin barrier recovery, and by histological assessment of the disrupted skin one week after moisturizer application.

Results: Overall, TEWL was reduced, epidermal thickness was lower, stratum corneum thickness was greater and the intensity of the dermal inflammatory infiltrate was reduced for treated sites.

Conclusions And Clinical Importance: These results suggest a potential benefit of the moisturizer for improving skin barrier function, which is frequently altered in chronic inflammatory dermatoses such as cAD.
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http://dx.doi.org/10.1111/vde.12859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586792PMC
October 2020

Long-term successful treatment of a donkey with cutaneous lupus erythematous with methotrexate.

Vet Dermatol 2020 Aug 15;31(4):313-e78. Epub 2020 Apr 15.

Université Lumière Lyon 2, VetAgro Sup, UP Interactions Cellules Environnement, 1 Avenue Bourgelat, 69280, Marcy l'Etoile, France.

Cutaneous lupus erythematosus (CLE) is a rare immune-mediated dermatitis. To the best of the authors' knowledge it has not been described in donkeys. A 5-year-old male neutered donkey, living in south-east France, was diagnosed with CLE. Clinical signs included generalized symmetrical areas of alopecia, erythema, crusting and scales. Diagnostic tests included examination of skin biopsy samples by histopathological and immunohistochemical analysis which demonstrated an interface dermatitis with CD8+ T cells. The skin condition was successfully treated initially with glucocorticoids and methotrexate; successful long-term maintenance was associated with administration of methotrexate.
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http://dx.doi.org/10.1111/vde.12847DOI Listing
August 2020

Pharmacokinetics of low-dose methotrexate in horses.

J Vet Pharmacol Ther 2020 Sep 26;43(5):461-469. Epub 2020 Mar 26.

Université de Lyon, VetAgro Sup, UPSP ICE 'Interactions Cellules Environnement', Marcy l'Etoile, France.

This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min  kg (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg  week may be safe and relevant in horses, although this has yet to be clinically confirmed.
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http://dx.doi.org/10.1111/jvp.12857DOI Listing
September 2020

Equine pastern vasculitis in a horse associated with a multidrug-resistant Pseudomonas aeruginosa isolate.

Vet Dermatol 2020 Jun 12;31(3):247-e55. Epub 2020 Jan 12.

UP Interactions Cellules Environnement, VetAgro Sup, Université de Lyon, 1 Avenue Bourgelat, 69280, Marcy l'Etoile, France.

Background: Equine pastern vasculitis is an uncommon disorder in horses. Underlying causes are difficult to assess, especially bacterial infections.

Clinical Summary: A 13-year-old French saddle gelding horse presented for evaluation of a six weeks history of pastern dermatitis. Histopathological examination of skin biopsy samples revealed small vessel vasculitis. A pure growth of a multidrug-resistant Pseudomonas aeruginosa (MRPA) was obtained from a deep skin biopsy. Clinical remission was observed after a six week course of enrofloxacin and lesions did not recur.

Conclusions And Clinical Importance: To the best of the authors' knowledge, this is the first report of a pastern vasculitis associated with MRPA and successfully treated with a six week course of enrofloxacin.
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http://dx.doi.org/10.1111/vde.12830DOI Listing
June 2020

In situ synthesis of FeO nanoparticles coated by chito-oligosaccharides: physico-chemical characterizations and cytotoxicity evaluation for biomedical applications.

Nanotechnology 2020 Apr 8;31(17):175602. Epub 2020 Jan 8.

IMP, CNRS UMR 5223, Univ Claude Bernard Lyon 1, Univ Lyon, 15 bd Latarjet, F-69622 Villeurbanne, France.

FeO nanoparticles coated with chito-oligosaccharides (COS) were prepared in situ by a simple co-precipitation method through a mixing of iron ions (Fe and Fe) and COS aqueous solutions followed by precipitation with ammonia. The impact of COS with different degree of polymerization (DP 10, 24 and 45) and degree of N-acetylation (DA) ∼ 24% and 50% (exhibiting high solubility) on the synthesis and physical properties of the coated magnetic nanoparticles was evaluated. Several advantages were found when the magnetic nanoparticles were prepared in the presence of the studied COS, such as: preparation of functionalized magnetic nanoparticles with narrower size distributions and, consequently, higher saturation magnetization (an increase of up to 22%); and an expressive increasing in the concentration of COS-coated magnetic nanoparticles (up to twice) in the cell viability test in comparison with pure FeO nanoparticles. Furthermore, among the analyzed samples, the magnetic nanoparticles coated by COS with DA ∼ 50% present a higher cytocompatibility. Our results allow envisioning various biomedical applications, valorizing the use of coated-magnetic nanoparticles for magnetic-field assisted drug delivery, enzyme or cell immobilization, or as a marker for specific cell tracking, among others.
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http://dx.doi.org/10.1088/1361-6528/ab68f9DOI Listing
April 2020

Granulomatous mural folliculitis in a dog treated with ciclosporin and methotrexate.

Vet Dermatol 2020 Apr 6;31(2):170-174. Epub 2020 Jan 6.

VetAgro Sup, UP Interactions Cellules Environnement, Université de Lyon, 1 Avenue Bourgelat, 69280, Marcy l'Etoile, France.

Background: Canine granulomatous mural folliculitis is a very rare cause of scarring alopecia with unknown pathogenesis.

Hypothesis/objectives: To report a case of granulomatous mural folliculitis in a dog treated with ciclosporin (Cs) and methotrexate (MTX).

Animal: A 13-year-old spayed female Pyrenean shepherd dog with a one month history of scarring alopecia.

Methods And Results: Histopathological examination revealed a granulomatous and lymphocytic mural and necrotizing folliculitis and furunculosis. Immunochemistry, using antibodies for CD3, CD204, CD206, IBA-1 and CD208, revealed that CD3 lymphocytes were infiltrating the outer root sheath along with IBA-1 or CD204 cells. Ciclosporin (5 mg/kg once daily) and MTX (0.25 mg/kg once weekly then 0.5 mg/kg once weekly) were initiated simultaneously, and Cs was stopped after stabilization of the lesions. The dog's skin disease was stable for six months.

Conclusions And Clinical Importance: To the best of the authors' knowledge, this is the first report of the long-term management of a granulomatous mural folliculitis in a dog. Ciclosporin and MTX appeared to be an effective treatment option. Additional treated cases are needed to assess the effectiveness of MTX in canine immune-mediated diseases.
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http://dx.doi.org/10.1111/vde.12825DOI Listing
April 2020

Highly Reduced Genome of the New Species , the Causative Agent of Nodular Thelitis and Tuberculoid Scrotitis in Livestock and a Close Relative of the Leprosy Bacilli.

mSphere 2018 10 3;3(5). Epub 2018 Oct 3.

Institut des Agent infectieux, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France

Nodular thelitis is a chronic enzootic infection affecting dairy cows and goats. The causative agent was recently shown to be related to the leprosy-causing bacilli and In this study, the genome of this pathogen was sequenced and analyzed. Phylogenomic analyses confirmed that the pathogen present in nodular thelitis and tuberculoid scrotitis is a distinct species related to the leprosy bacilli and Because the pathogen was originally isolated from a bovine udder, it was named "" The genome of "" is only 3.12 Mb in length, which represents the smallest mycobacterial genome identified so far but which is close to that of leprosy bacilli in size. The genome contains 1,759 protein-coding genes and 1,081 pseudogenes, indicative of extensive reductive evolution and likely the reason that cannot be grown axenically. The pseudogenization and genome reduction in seem to have been to some extent independent from the results determined for the genomes of the leprosy bacilli. is an emerging skin pathogen in dairy animals. Its genome underwent massive reduction and gene decay, leading to a minimal set of genes required for an obligatory intracellular lifestyle, which highly resembles the evolution of the leprosy agents and The genomic similarity between and the leprosy bacilli can help in identifying key virulence factors of these closely related species or in identifying genes responsible for the distinct differences between thelitis or scrotitis and leprosy with respect to clinical manifestations. Specific DNA markers can now be developed for quick detection of this pathogen.
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http://dx.doi.org/10.1128/mSphere.00405-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170788PMC
October 2018

Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe.

Parasit Vectors 2018 Sep 10;11(1):506. Epub 2018 Sep 10.

Boehringer Ingelheim Animal Health, 29 avenue Tony Garnier, 69007, Lyon, France.

Background: A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland.

Methods: Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions.

Results: Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment.

Conclusions: This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.
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http://dx.doi.org/10.1186/s13071-018-3083-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131853PMC
September 2018

Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin.

J Histochem Cytochem 2019 02 10;67(2):85-97. Epub 2018 Sep 10.

UDEAR, INSERM, University of Toulouse, Toulouse, France.

Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Our aim was to better characterize the distribution of FLG and CDSN in canine skin. Using immunohistochemistry on beagle skin, we screened a series of monoclonal antibodies (mAbs) specific for human FLG and CDSN. The cross-reactive mAbs were further used using immunoelectron microscopy and Western blotting. The structure of canine CDSN and FLG was determined using publicly available databases. In the epidermis, four anti-FLG mAbs stained keratohyalin granules in the granular keratinocytes and corneocyte matrix of the lower cornified layer. In urea-extracts of dog epidermis, several bands corresponding to proFLG and FLG monomers were detected. One anti-CDSN mAb stained the cytoplasm of granular keratinocytes and cells of both the inner root sheath and medulla of hair follicles. Dog CDSN was located in lamellar bodies, in the extracellular parts of desmosomes and in corneodesmosomes. A protein of 52 kDa was immunodetected. Genomic DNA analysis revealed that the amino acid sequence and structure of canine and human CDSN were highly similar.
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http://dx.doi.org/10.1369/0022155418798807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354317PMC
February 2019

Pharmacokinetics of low-dose methotrexate in healthy beagle dogs.

J Vet Pharmacol Ther 2018 Oct 12;41(5):659-669. Epub 2018 Jun 12.

Interaction Cellule Environnement, Unité Pharmacologie et Toxicologie, VetAgro Sup-Campus Vétérinaire de Lyon, Marcy l'Etoile, France.

Methotrexate may be an alternative to ciclosporin in the treatment of canine atopic dermatitis (cAD) as suggested by recent data. The aim of the study was to investigate both the tolerance and the pharmacokinetic behavior of methotrexate (MTX) in plasma, following intravenous (i.v.), subcutaneous (s.c.) or oral (OR) administration over several weeks. Six healthy dogs were given oral MTX once a week, respectively, per dog at 2.5 mg/1 week, 5 mg/4 weeks, 7.5 mg/3 weeks, 10 mg/6 weeks and 12.5 mg/5 weeks. No clinically relevant abnormalities of laboratory parameters were noticed. A high inter-individual variation of MTX plasma concentration was observed with a suspicion of saturation phenomenon in absorption. To compare with other routes of administration, six healthy beagle dogs followed a crossover design study at 7.5 mg per dog MTX. The absolute bioavailability was 93% for SC injection and 30% for the oral route. The inter-individual variability was quite low following SC administration compared to oral route. Just as in human, given the substantial variability of oral absorption, clinicians cannot assume consistent oral bioavailability of MTX. Therefore, they may consider switching dogs to the SC route in case of absence of clinical response with a weekly oral dose.
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http://dx.doi.org/10.1111/jvp.12673DOI Listing
October 2018

Skin lesions in Aubrac cows strongly associated with fly bites (Haematobia irritans).

Vet Dermatol 2018 Jun 1;29(3):254-e94. Epub 2018 Mar 1.

UP Interactions Cellules Environnement, VetAgro Sup, Université de Lyon, 1 Avenue Bourgelat, 69280, Marcy l'Etoile, France.

Background: The horn fly Haematobia irritans is known to cause problems in cattle including weight loss and decreased milk production; cutaneous lesions have not been widely reported and descriptions of the clinical manifestations are quite variable.

Hypothesis/objectives: This study describes the clinical and histopathological lesions of several Aubrac cows that presented with focal to confluent areas of alopecia, skin scaling and thickening, suspected to be induced by H. irritans bites.

Animals: Twenty seven, three- to six-year-old Aubrac cows, kept in mountain pastures in France, that presented with an apparently asymptomatic alopecic dermatosis.

Methods: Samples for skin cytological evaluation, skin scrapings and trichograms were examined; also, skin biopsy specimens from affected animals were used for histopathological examination.

Results: Clinical lesions consisted of focal to coalescing, symmetrical areas of hair loss and scaling, located on the back, flanks, and lateral and caudal aspects of the thighs. Histopathological examination revealed perivascular, oedematous, eosinophilic dermatitis with eosinophilic folliculitis and furunculosis. Species identification of several flies captured on the cows revealed H. irritans. The final clinicopathological diagnosis was eosinophilic dermatitis and folliculitis and furunculosis, suspected to be due to H. irritans fly-bite.

Conclusion And Clinical Importance: Fly-bite (H. irritans) dermatitis should be included in the differential diagnosis of alopecic dermatoses in cows.
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http://dx.doi.org/10.1111/vde.12530DOI Listing
June 2018

Clinical and histopathological aspects of an alopecia syndrome in captive Andean bears (Tremarctos ornatus).

Vet Dermatol 2018 Jun 31;29(3):234-e85. Epub 2018 Jan 31.

VetAgro Sup, UP Interactions Cellules Environnement, Univ Lyon, 1 Avenue Bourgelat, 69280, Marcy l'Etoile, France.

Background: Captive Andean bears (Tremarctos ornatus) develop a distinct alopecic syndrome of unknown aetiology.

Hypothesis/objectives: To describe the histological features of healthy Andean bear skin, to define the clinical and histopathological features of Andean bears with signs of alopecia, and to propose an aetiopathogenesis.

Animals: Eighteen healthy Andean bears housed in 12 European zoos and 13 Andean bears with mild to severe alopecia housed in nine European zoos.

Methods: Two surveys describing signalment and clinical features of affected bears; follicular density was measured in a single healthy bear using a dermatoscope; cytological samples were collected by tape stripping from two healthy and three alopecic bears; skin biopsies were collected for histological evaluation from healthy and alopecic bears; immunohistochemistry (CD3, AE1/AE3 cytokeratins) was performed when lymphocytic inflammation was observed.

Results: The syndrome is an acquired, slowly progressive alopecia. Bears are otherwise healthy. Histological features include a dermal inflammatory infiltrate composed of T lymphocytes and eosinophils; atrophy of hair follicles at the level of or below the isthmus, and lymphocytic infiltration of hair follicles and the epidermis. Multinucleated giant cells were present in the outer root sheaths of hair follicles in five bears.

Conclusion And Clinical Importance: Andean bear alopecia syndrome is an acquired, progressive alopecia with histological features consistent with a lymphocytic immune-mediated reaction directed against follicular sheaths and the epidermis. Trigger factors have not been identified. Further studies are indicated to define the features of this multifactorial syndrome.
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http://dx.doi.org/10.1111/vde.12522DOI Listing
June 2018

TREATMENT SUCCESS IN THREE ANDEAN BEARS (TREMARCTOS ORNATUS) WITH ALOPECIA SYNDROME USING OCLACITINIB MALEATE (APOQUEL®).

J Zoo Wildl Med 2017 09;48(3):818-828

Andean bear (Tremarctos ornatus) alopecia syndrome (ABAS) commonly affects captive bears, particularly sexually mature females. ABAS is characterized by bilaterally symmetrical predominantly flank alopecia with or without profound pruritus and secondary bacterial and Malassezia infections. There is no effective treatment and severely affected bears have been euthanized. This paper describes the successful management of ABAS in three female Andean bears. Skin biopsies and cytology revealed a mixed dermal inflammatory infiltrate, alopecia, hyperkeratosis, and Malassezia dermatitis. Allergen specific serology was positive for environmental allergens in one case. Hematology, serum biochemistry, and thyroid and adrenal function were normal in all cases. There was no consistent response to novel diet trials, antifungals, antihistamines, allergen specific immunotherapy, or topical antimicrobials. There was a partial response to ciclosporin (Atopica® cat, Novartis Animal Health; 5 mg/kg po, sid) in one case and oral glucocorticoids in all cases (dexamethasone sodium phosphate, [Colvasone 0.2%, Norbrook], 0.15 mg/kg po, sid or prednisolone [Deltacortene, Bruno Farmaceutici, and Megasolone 20, Coophavet], 0.3-1.2 mg/kg po, sid), but treatment was withdrawn following adverse effects. Treatment with oclacitinib maleate (Apoquel®, Zoetis; 0.46-0.5 mg/kg po, bid) resulted in rapid and complete resolution of the pruritus with subsequent improvement in demeanor and fur regrowth. After 5 mo, the bears were almost fully furred and off all other medication. Treatment was tapered to the lowest dose that prevented relapse of the pruritus (0.23-0.4 mg/kg po, sid). No adverse effects have been noted. ABAS is usually an intractable condition, and, to our knowledge, oclacitinib is the first treatment shown to result in sustained clinical improvement. Further studies on the etiology of ABAS, and on efficacy and long-term safety of oclacitinib are needed.
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http://dx.doi.org/10.1638/2016-0239.1DOI Listing
September 2017

Successful medical treatment of an Aspergillus terreus mycetoma of the nostril/lip in a 16-year-old Fjord pony gelding with pituitary pars intermedia dysfunction.

Vet Dermatol 2017 Dec 23;28(6):629-e155. Epub 2017 Jul 23.

VetAgro Sup, Veterinary Campus of Lyon, University of Lyon, 69280, Marcy l'Etoile, France.

Background: Mycetoma is a chronic, proliferative lesion of cutaneous/subcutaneous tissue characterized by draining tracts and granules in the discharge caused by actinomycetes (actinomycetoma) or filamentous fungi (eumycotic mycetoma).

Objectives: This case report describes the unusual finding of a cutaneous mycetoma of the lateral wing of the right nostril in a gelding.

Animal: A 16-year-old Fjord gelding with suspected pituitary pars intermedia dysfunction (PPID) was presented for evaluation of a nonpainful, firm and raised mass involving the lateral wing of the right nostril and the lip.

Methods And Results: Cytological examination of the mass showed marked pyogranulomatous inflammation and histopathological examination revealed a fungal mycetoma. Fungal culture identified the causative organism as Aspergillus terreus, which is not known for its propensity to cause either dermal granulomas or mycetoma in domestic animals. Further investigation, including a TRH stimulation test, led to a diagnosis of PPID (Cushing's disease), which may have led to immunosuppression of the animal and increased susceptibility to infection.

Conclusions And Clinical Importance: The horse was treated medically with pergolide for the PPID and oral potassium iodide for the fungal infection, with good therapeutic response and no relapse after five months. Surgical debridement or excision was not performed. To the best of the authors' knowledge, this is the first case report of a cutaneous mycetoma caused by A. terreus in a horse.
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http://dx.doi.org/10.1111/vde.12471DOI Listing
December 2017

Non-dermatophyte Dermatoses Mimicking Dermatophytoses in Animals.

Authors:
Didier Pin

Mycopathologia 2017 Feb 16;182(1-2):113-126. Epub 2016 Nov 16.

UP Interactions Cellules Environnement, VetAgro Sup, Univ Lyon, 69280, Marcy l'Etoile, France.

Dermatophytoses in animals are fungal diseases of the skin caused by dermatophyte fungi of the genus Microsporum or Trichophyton. Because the infection is generally follicular, the most common clinical sign is one or many circular areas of alopecia with variable erythema, scaling and crusting, and the primary differential diagnoses are follicular infections, such as bacterial folliculitis and demodicosis. Although dermatophyte folliculitis or ringworm is the most commonly observed lesion of dermatophytoses in animals, other presentations may be observed according to the host species and the dermatophyte involved: dermatophyte folliculitis or ringworm, scaling and crusting in dermatophytosis due to Microsporum persicolor, nodule in case of kerion or mycetoma, matted hairs, seborrheic dermatosis or miliary dermatitis in cats, generalized exfoliative dermatoses in dogs, cats and horses, superficial non-follicular pustules, papules and macules in the Devon Rex cat, pruritic dermatophytoses in dogs, cats and horses, and onychomycosis in dogs, cats and horses. Since manifestations of dermatophytosis are highly variable, particularly in the cat, dermatophytosis should be considered in case of any annular, papular, nodular or pustular dermatoses, alopecic or not, sometimes pruritic, and nodular dermatoses as well.
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http://dx.doi.org/10.1007/s11046-016-0090-8DOI Listing
February 2017

Size dependent skin penetration of nanoparticles in murine and porcine dermatitis models.

Eur J Pharm Biopharm 2016 Mar 12;100:101-8. Epub 2016 Jan 12.

FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France; Department of Pharmaceutics, School of Pharmacy, University of Bonn, Bonn, Germany. Electronic address:

A major limitation in the current topical treatment of inflammatory skin diseases is the inability to selectively deliver the drug to the inflammation site. Recently, smart drug delivery systems such as nanocarriers are being investigated to enhance the selective deposition of anti-inflammatory drugs in inflamed areas of the skin to achieve higher therapeutic efficacy with minimal side effects. Of such systems, polymeric nanoparticles are considered very efficient carriers for the topical drug delivery. In the current work, poly(l-lactide-co-glycolide) nanoparticles of nominal sizes of 70nm (NP70) and 300nm (NP300) were studied for their intra-epidermal distribution in murine and pig atopic dermatitis models over time against the respective healthy controls. Confocal laser scanning microscopical examination of skin biopsies was utilized for the qualitative and semi-quantitative analyses of nanoparticles skin deposition and penetration depth. While no skin penetration was found for any of the particles in healthy skin, the accumulation of NP70 was significantly higher than NP300 in inflamed skin (15-fold in mice, 5-fold in pigs). Penetration depth of NP70 decreased over time in mice from 55±3μm to 20±2μm and similar tendencies were observed for the other formulations. In inflamed pig skin, a similar trend was found for the penetration depth (NP70: 46±12μm versus NP300: 23±3μm); however, the NP amount remained constant for the whole analyzed period. Their ability to penetrate specifically into inflamed skin combined with minimal effects on healthy skin underlines small polymeric nanoparticles' potential as selective drug carriers in future treatment of chronic inflammatory skin diseases such as atopic dermatitis.
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http://dx.doi.org/10.1016/j.ejpb.2016.01.002DOI Listing
March 2016

Whole-genome sequencing identifies a homozygous deletion encompassing exons 17 to 23 of the integrin beta 4 gene in a Charolais calf with junctional epidermolysis bullosa.

Genet Sel Evol 2015 May 3;47:37. Epub 2015 May 3.

INRA, UMR1313 Génétique Animale et Biologie Intégrative, domaine de Vilvert, Jouy-en-Josas, F-78352, France.

Background: Since 2010, four Charolais calves with a congenital mechanobullous skin disorder that were born in the same herd from consanguineous matings were reported to us. Clinical and histopathological examination revealed lesions that are compatible with junctional epidermolysis bullosa (JEB).

Results: Fifty-four extended regions of homozygosity (>1 Mb) were identified after analysing the whole-genome sequencing (WGS) data from the only case available for DNA sampling at the beginning of the study. Filtering of variants located in these regions for (i) homozygous polymorphisms observed in the WGS data from eight healthy Charolais animals and (ii) homozygous or heterozygous polymorphisms found in the genomes of 234 animals from different breeds did not reveal any deleterious candidate SNPs (single nucleotide polymorphisms) or small indels. Subsequent screening for structural variants in candidate genes located in the same regions identified a homozygous deletion that includes exons 17 to 23 of the integrin beta 4 (ITGB4), a gene that was previously associated with the same defect in humans. Genotyping of a second case and of six parents of affected calves (two sires and four dams) revealed a perfect association between this mutation and the assumed genotypes of the individuals. Mining of Illumina BovineSNP50 Beadchip genotyping data from 6870 Charolais cattle detected only 44 heterozygous animals for a 5.6-Mb haplotype around ITGB4 that was shared with the carriers of the mutation. Interestingly, none of the 16 animals genotyped for the deletion carried the mutation, which suggests a rather recent origin for the mutation.

Conclusions: In conclusion, we successfully identified the causative mutation for a very rare autosomal recessive mutation with only one case by exploiting the most recent DNA sequencing technologies.
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http://dx.doi.org/10.1186/s12711-015-0110-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417276PMC
May 2015

Mycobacterium species related to M. leprae and M. lepromatosis from cows with bovine nodular thelitis.

Emerg Infect Dis 2014 Dec;20(12):2111-4

Bovine nodular thelitis is a granulomatous dermatitis associated with infection with acid-fast bacteria. To identify the mycobacterium responsible for this infection, we conducted phylogenetic investigations based on partial sequencing of 6 genes. These bacteria were identified as an undescribed Mycobacterium species that was phylogenetically related to M. leprae and M. lepromatosis.
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http://dx.doi.org/10.3201/eid2012.140184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257800PMC
December 2014

The syndecan binding sequence KKLRIKSKEK in laminin α3 LG4 domain promotes epidermal repair.

Eur J Dermatol 2013 Apr 9. Epub 2013 Apr 9.

SFR BioSciences Gerland-Lyon Sud, Institut de biologie et chimie des protéines, UMR 5305, CNRS; Université Lyon 1, 7 passage du Vercors, 69367, Lyon, France.

Epithelialization of normal wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore the barrier function. Keratinocyte migration is one of the most earliest and crucial event determining the efficiency of the overall wound repair process. Laminin 332, composed by the association of α3, β3 and γ2 chains, is a major adhesion substrate for keratinocytes and is known for its role in supporting cell adhesion and migration during wound repair. The α3 chain comprises a large globular region in its carboxyl-terminal end, which consists of five homologous globular domains (LG1-LG5), known to be involved in cellular interactions. Recent findings have suggested that the α3 chain C-terminal domains LG45 may have a role to play during the epithelialization phase in wound repair. In the present study, we have analyzed whether a peptide mimicking the major heparin binding sequence KKLRIKSKEK in α3LG45 may interact with keratinocytes to promote cell adhesion and migration. In vitro experiments supported this hypothesis and revealed that the KKLRIKSKEK peptide induces human primary keratinocyte adhesion and has the ability to promote keratinocyte migration when added in the culture medium. To examine the peptide efficacy in vivo, the KKLRIKSKEK peptide was applied over partial-thickness cutaneous wounds in pigs. Compared with vehicle-treated cutaneous wounds, the peptide application significantly promoted early-stage wound healing by accelerating re-epithelialization. Additional beneficial effects such as reduced inflammatory response and decreased granulation tissue formation were also noticed in the peptide-treated wounds.
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http://dx.doi.org/10.1684/ejd.2013.1974DOI Listing
April 2013

PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans.

Nat Genet 2012 Jan 15;44(2):140-7. Epub 2012 Jan 15.

Centre National de la Recherche Scientifique, Institut de Génétique et Développement de Rennes, Rennes, France.

Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.
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http://dx.doi.org/10.1038/ng.1056DOI Listing
January 2012

Characterization of the canine skin barrier restoration following acute disruption by tape stripping.

Vet Dermatol 2012 Apr 21;23(2):103-9, e23. Epub 2011 Dec 21.

Unité Dermatologie, VetAgro Sup Campus Vétérinaire de Lyon, Marcy l'Etoile F-69280, France.

The stratum corneum (SC) forms the main part of the permeability barrier of the skin. In mice and in humans, cutaneous barrier disruption can be generated by removing the SC with tape stripping (TS) and the skin barrier function can be assessed by measurement of transepidermal water loss (TEWL). The aim of the present study was to characterize the skin barrier restoration in the dog following mechanical disruption and to analyse the correlation between the skin barrier recovery and TEWL measurement. Thirty sequential TS were performed on 12 sites on four healthy beagle dogs. The number of TS was chosen to ensure a sufficient barrier disruption with a slow recovery. Skin repair was assessed for 72 h by clinical and histological examinations, and TEWL measurements. The results showed that performing 30 TS was adequate to disrupt the skin barrier in the dog. The homeostatic repair response, initiated in the skin, was rapid and characterized by complete restoration of the SC within 72 h, accompanied by greater basal cell proliferation, and dermal eosinophilic inflammation. TEWL was significantly increased by complete removal of the SC but recovered along with restoration of the SC (Scheffe test, P ≤ 0.05). Characterization of a canine model of barrier disruption and restoration and assessment of the skin barrier function by TEWL measurements could help better understand the events implied in skin barrier function. Development of this canine model is also necessary for future studies on the effects of treatments aimed at restoring the skin barrier.
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http://dx.doi.org/10.1111/j.1365-3164.2011.01019.xDOI Listing
April 2012

Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis.

Vet Dermatol 2012 Feb 7;23(1):45-50, e11. Epub 2011 Sep 7.

Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.
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http://dx.doi.org/10.1111/j.1365-3164.2011.01006.xDOI Listing
February 2012

Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study.

Vet Res Commun 2011 Dec 23;35(8):501-9. Epub 2011 Jul 23.

Laboratory for Dermatological Research EA4169 "Normal and Pathological Functions of the Skin Barrier", Université Lyon 1, Lyon, France.

Alterations of the lipid expression in the skin of human and canine atopic subjects may be one of the key factors in the disease development. We have analyzed the ultrastructure of the clinically uninvolved skin of atopic dogs and compared it with the lipid composition of their tape-stripped stratum corneum (SC). The effect of a 2 month treatment of atopic dogs by food supplementation with a mixture of essential fatty acids was evaluated on skin samples taken before and after the treatment period. Electron microscopy revealed that the non-lesional skin of atopic dogs exhibited an abnormal and largely incomplete structure of the lamellar lipids with little cohesion between the corneocyte strata. The SC of atopic dogs was characterized by a significant decrease in the lipid content when compared to the healthy controls. Following oral supplementation with the mixture of essential fatty acids, the overall lipid content of the SC markedly increased. This feature was observed both with the free and, most importantly, with the protein-bound lipids (cholesterol, fatty acids and ceramides), the latter constituting the corneocyte-bound scaffold for ordinate organisation of the extracellular lipid bi-layers. Indeed, the semi-quantitative electron microscopy study revealed that the treatment resulted in a significantly improved organization of the lamellar lipids in the lower SC, comparable to that of the healthy dogs. Our results indicate the potential interest of long-term alimentary supplementation with omega-6 and omega-3 essential fatty acids in canine atopic dermatitis.
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http://dx.doi.org/10.1007/s11259-011-9493-7DOI Listing
December 2011

Correction of dog dystrophic epidermolysis bullosa by transplantation of genetically modified epidermal autografts.

J Invest Dermatol 2011 Oct 23;131(10):2069-78. Epub 2011 Jun 23.

INSERM, U634, Nice, France.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering condition caused by mutations in the gene coding for collagen type VII. Genetically engineered RDEB dog keratinocytes were used to generate autologous epidermal sheets subsequently grafted on two RDEB dogs carrying a homozygous missense mutation in the col7a1 gene and expressing baseline amounts of the aberrant protein. Transplanted cells regenerated a differentiated and vascularized auto-renewing epidermis progressively repopulated by dendritic cells and melanocytes. No adverse immune reaction was detected in either dog. In dog 1, the grafted epidermis firmly adhered to the dermis throughout the 24-month follow-up, which correlated with efficient transduction (100%) of highly clonogenic epithelial cells and sustained transgene expression. In dog 2, less efficient (65%) transduction of primary keratinocytes resulted in a loss of the transplanted epidermis and graft blistering 5 months after transplantation. These data provide the proof of principle for ex vivo gene therapy of RDEB patients with missense mutations in collagen type VII by engraftment of the reconstructed epidermis, and demonstrate that highly efficient transduction of epidermal stem cells is crucial for successful gene therapy of inherited skin diseases in which correction of the genetic defect confers no major selective advantage in cell culture.
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http://dx.doi.org/10.1038/jid.2011.172DOI Listing
October 2011

Clinical characteristics and causes of pruritus in cats: a multicentre study on feline hypersensitivity-associated dermatoses.

Vet Dermatol 2011 Oct 15;22(5):406-13. Epub 2011 Mar 15.

Dermatology Department, Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Hypersensitivity dermatitides (HD) are often suspected in cats. Cats with HD are reported to present with one or more of the following patterns: miliary dermatitis, eosinophilic dermatitis, self-induced symmetrical alopecia or head and/or neck excoriations. Previous reports on feline HD included small numbers of animals, took place in geographically restricted areas or did not compare these conditions with other causes of pruritus. The goal of the present study was to analyse 72 parameters covering signalment, clinical, laboratory and treatment characteristics from a large group of pruritic cats from different geographical areas. Of the 502 cats, the following diagnoses were made: flea HD (29% of cases), food HD (12%) nonflea/nonfood HD (20%) and other diseases in which pruritus was a feature (24%). Cats with signs consistent with a HD but which did not complete a food trial were not analysed further (15% of cases). Most cats with nonflea HD exhibited signs compatible with one or more of the four typical lesional patterns, but none of these patterns was found to be pathognomonic for any specific diagnosis. Food HD and nonflea/nonfood HD were found to be clinically undistinguishable. Young adult, purebred and female cats appeared predisposed to nonflea/nonfood HD. As many diagnoses presented with similar lesional patterns, a thorough clinical work-up is required for establishment of a specific diagnosis.
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http://dx.doi.org/10.1111/j.1365-3164.2011.00962.xDOI Listing
October 2011

First description of onychomycosis caused by Chrysosporium keratinophilum in captive Bennett's wallabies (Macropus rufogriseus rufogriseus).

J Zoo Wildl Med 2011 Mar;42(1):156-9

Unité Dermatologie-VetAgro Sup Campus Vétérinaire de Lyon, F-69280 Marcy l'Etoile, France.

Seven Bennett's wallabies (Macropus rufogriseus rufogriseus) presented within a period of several months with onychodystrophy, onychomadesis, and severe digital tumefaction. Histopathologic findings included a pseudocarcinomatous hyperplasia of the claw matrix surrounding a cavity filled with keratin and septate hyphae stained with periodic acid Schiff reagent. The fungal species Chrysosporium keratinophilum was identified on cultures. The wallabies were orally treated with ketoconazole (15 mg/kg s.i.d.) for 20 wk. Material and enclosures were cleaned and sprayed with 0.2% enilconazole solution once a month over a period of 4 mo. No improvement of advanced cases was observed, but no new case appeared for the next 6 mo. The positive mycological culture and the invasion of tissues on histopathologic examination suggested that the fungal species C. keratinophilum was implicated in this claw disease. This is the first report of onychomycosis caused by C. keratinophilum in animals.
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http://dx.doi.org/10.1638/2010-0129.1DOI Listing
March 2011

Atopic dermatitis in dogs is associated with a high heterogeneity in the distribution of protein-bound lipids within the stratum corneum.

Arch Dermatol Res 2011 Aug 15;303(6):433-40. Epub 2011 Jan 15.

Laboratory of Dermatological Research, EA 4169, Edouard Herriot Hospital, University of Lyon-I, Lyon, France.

The stratum corneum (SC) was taken from five atopic dogs by tape stripping (12 strips) of non-lesional areas of the abdomen. The free and protein-bound lipids were extracted and analyzed by thin-layer chromatography after fractionation on aminopropyl-bonded silica gel columns. A very frequent feature was the heterogeneity in the lipid content of consecutive layers. This was even more accentuated for the covalently bound lipids, with variations from one layer to another in the concentrations of cholesterol, omega hydroxylated ceramides and omega hydroxylated long-chain fatty acids. Among the free lipids, large amounts of glucosylceramides were present in canine atopic SC although they are nearly absent from the SC of normal dogs. A heterogeneous distribution of lipids was seen in canine atopic SC. These results suggest that strikingly deep variations occur in the lipid metabolism of keratinocytes in the skin of atopic dogs. In order to gain insight into this phenomenon, further studies should be focused on the activity of enzymes involved in both biosynthetic and catabolic processes.
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http://dx.doi.org/10.1007/s00403-011-1120-5DOI Listing
August 2011

Analysis of free and protein-bound ceramides by tape stripping of stratum corneum from dogs.

Arch Dermatol Res 2010 Nov 2;302(9):639-44. Epub 2010 Apr 2.

Laboratory of Dermatological Research, EA 4169 University of Lyon-I and Edouard Herriot Hospital, Lyon, France.

The free and protein-bound ceramides of dog stratum corneum (SC) were analyzed by thin-layer chromatography after tape stripping of the abdomen of five dogs. The sphingoid bases were identified by gas-liquid chromatography as sphingosine, phytosphingosine, and 6-hydroxysphingosine. Electrospray ionization-ion trap mass spectrometry was used to characterize the protein-bound ceramides containing sphingosine and omega-hydroxy long-chain fatty acids. Although the molecular species were the same ones in all dogs, wide quantitative variations in the patterns of SC ceramides were observed in different breeds of dogs. The free ceramide concentration changed with the depth of SC, with a higher concentration in the deep layers, whereas the concentration of protein-bound ceramides remained constant. These results show that canine SC is close to that of humans with respect to ceramides.
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http://dx.doi.org/10.1007/s00403-010-1049-0DOI Listing
November 2010