Hereditary nasal parakeratosis in Labrador ... - Wiley Online Library

Veterinary Dermatology 2003, 14, 103 – 110

Case report

Blackwell Science, Ltd

Hereditary nasal parakeratosis in Labrador Retrievers NADIA PAGÉ*, MANON PARADIS†, JEAN-MARTIN LAPOINTE‡ and ROBERT W. DUNSTAN§ *Veterinary Teaching Hospital, †Department of Clinical Sciences and ‡Department of Pathology and Microbiology, Faculté de médecine vétérinaire, University of Montreal, C.P. 5000, St-Hyacinthe, J2S 7C6, Canada §Department of Pathobiology, Texas A & M University, College Station, USA (Received 27 November 2001; accepted 23 July 2002)

Abstract Hereditary nasal dermatitis is reported in 14 Labrador Retrievers and 4 Labrador Retriever crosses. This appears to be a newly described inherited disorder for which an autosomal recessive mode of inheritance is suspected. The lesions were first noted between 6 and 12 months of age. Histopathological analysis revealed parakeratotic hyperkeratosis, often with marked multifocal accumulation of proteinaceous fluid between keratinocytes within the stratum corneum and superficial stratum spinosum. There was also a sub-basal lymphoplasmacytic infiltration within the superficial dermis. Immunohistochemistry staining for IgG (n = 4), distemper and papillomaviruses (n = 4) were negative, as were serum antinuclear antibody serology (n = 4) and fungal culture (n = 7). Electron microscopy revealed an altered cornification process: retention of nuclear chromatin, absence of lamellar bodies and marked intercellular oedema. Dogs did not respond to oral administration of zinc methionin (n = 3), cephalexin (n = 4), vitamin A alcohol (n = 1) or topical tretinoin (n = 1). Improvement of the lesions was obtained with topical vitamin E (n = 2), petroleum jelly (n = 2), and propylene glycol (n = 5). Keywords: canine, cornification disorder, hereditary disorder, Labrador Retriever, nasal dermatitis, nasal parakeratotic hyperkeratosis.

INTRODUCTION There are several known causes of nasal hyperkeratosis in dogs. They include distemper, pemphigus foliaceus or erythematosus, discoid or systemic lupus erythematosus, zinc-responsive dermatosis, ichthyosis and necrolytic migratory erythema.1,2 There is also an idiopathic form of nasal hyperkeratosis that occurs most commonly in old dogs.1–3 A few years ago, one of the authors (MP) observed lesions of nasal hyperkeratosis with clinicopathological similarities in two Labrador Retrievers and one Labrador Retriever cross, prompting further investigation. The purpose of this study was to describe what appears to be a hereditary hyperkeratotic nasal dermatitis of early onset as observed in several Labrador Retrievers and Labrador Retriever crosses originating from different breeders.

METHODS Data were obtained from the owners and breeders of affected dogs in Quebec, Canada and from Vermont, USA. Dogs were selected based on compatible clinical

Correspondence: Nadia Pagé. E-mail: [email protected] © 2003 European Society of Veterinary Dermatology

signs and history. Nine dogs were examined at the veterinary teaching hospital of the University of Montreal and one case was seen by a veterinary dermatologist in a private practice in Montreal. The clinical presentation of the disease was recorded, as was information regarding other affected and unaffected relatives. This permitted us to retrieve eight additional affected dogs. Pedigrees were obtained when possible. Nasal planum biopsies, taken from ten dogs (six Labrador Retrievers, four Labrador Retriever crosses), were processed routinely for histopathology (haematoxylin/phloxin/saffron staining in all cases, Gram and PAS stains in four cases, Masson’s trichrome stain in seven cases). Different immunohistochemical staining techniques were carried out on the tissue: canine IgG (direct immunoperoxidase; n = 4), canine distemper virus (avidin–biotin complex peroxidase technique, using a rabbit polyclonal antibody to measles virus, and a monoclonal anticanine distemper virus antibody, n = 4) and papillomaviruses (avidin–biotin complex peroxidase technique, using a rabbit polyclonal antibody to bovine papilloma virus; n = 4; Department of Veterinary Microbiology, Western College of Veterinary medicine, Saskatoon, Canada). Ultrastructural examination was performed on biopsy samples from two dogs. Both biopsy samples were fixed in 10% neutral-buffered formalin, post fixed in 1.3% osmium tetroxide and embedded in epoxy resin (Ted Pella, 103

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Figure 1. Ancestor tree of Labrador Retrievers with hyperkeratotic nasal dermatitis.

Redding, CA). Ultrathin sections were stained with uranyl acetate and lead citrate and examined using a Phillips 300 electron microscope. Fungal cultures from the lesions were performed in seven dogs (Fungassay®, Synbiotics Corp., San Diego, CA). Antinuclear antibody serology (ANA) was performed in four dogs. A CBC and biochemistry profile were carried out in three dogs. Various treatment modalities were attempted in several dogs, and response was assessed by physical examination when possible, or by telephone follow-up.

RESULTS Familial history and clinical findings Fourteen Labrador Retrievers, coming from four different litters were retrieved. Four additional Labrador Retriever crosses came from a breeding colony. These four dogs came from four different litters, and for each litter, the dam was a Labrador Retriever, and the sire a Labrador–Bernese Mountain Dog cross. There were 5 females and 13 males. Affected dogs were either

yellow, black or chocolate. Available pedigree analyses revealed that 16/18 dogs shared common ancestors (Fig. 1). The co-ancestry coefficients between affected litters varied from 0.01 to 0.17, and the inbreeding coefficients, between 0.004 and 0.14. None of the sires or dams of affected dogs were clinically affected. In all cases, nasal hyperkeratotic lesions were noticed between 6 and 12 months of age. They varied in severity from mild to severe. They typically affected the dorsal aspect of the nasal planum, and consisted of greyish or brownish adherent accumulations of dry and rough keratin (Figs 2 and 3). In the more severe cases, fissures and erosions occasionally developed. Sometimes the owners noticed that the hyperkeratosis was less severe, and became a paler shade of grey or brown after the dog’s nose was wetted by playing in water or snow. The owners did not notice worsening of the lesions with increased solar exposition. Some dogs had depigmentation of the remaining nasal planum (Fig. 4). Two additional dogs also presented with mild scaling and crusting lesions on the hairy part of the bridge of the nose, and one of these two dogs had footpad hyperkeratosis. One other dog had a history of footpad

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Figure 2. Hyperkeratosis on nasal planum. Labrador Retriever, 1.2 years old, case no. 1. Moderate accumulation of dry, rough keratin, mostly on the dorsal part of the nasal planum.

Figure 3. Nasal hyperkeratosis of a Labrador Retriever, 1.4 years old, case no. 3. Note the keratin projections on the dorsal part and the depigmentation of the lower portion of the nasal planum.

Figure 4. Hyperkeratosis on nasal planum of a Labrador Retriever, 3 years old, case no. 9. Note depigmentation and erythema of the lower portion of the nasal planum.

hyperkeratosis, but the footpads were normal upon presentation. All 18 dogs were otherwise healthy. Pathological findings The 10 biopsies revealed qualitatively similar changes. In all cases there was parakeratotic hyperkeratosis, varying from moderate to severe, with mild to moderate acanthosis (Fig. 5). All cases had areas of intercellular

Figure 5. Histological section of skin from a hyperkeratotic lesion on the nasal planum of a Labrador Retriever. There is a thick layer of parakeratotic hyperkeratosis, and intercellular accumulation of protein-rich fluid in the stratum corneum and superficial stratum spinosum, coalescing into a small vesicle in one area. The dermis shows mild sub-basal inflammatory cell infiltration, with pigmentary incontinence. Hematoxylin /phloxin /saffron, ×10.

Figure 6. Detail of epidermis from a hyperkeratotic lesion on the nasal planum of a Labrador Retriever. Note the parakeratosis and accumulations of intercellular fluid, some of which contain free neutrophils or cellular debris. A few keratinocytes of the superficial stratum spinosum show hydropic degeneration. Haematoxylin/ phloxin /saffron.

oedema (spongiosis) and accumulation of abundant proteinaceous fluid within the superficial stratum spinosum (Fig. 6); this fluid was periodic acid Schiff (PAS)-positive in the four cases that were PAS-stained. In the more severely affected areas there was formation of spongiotic vesicles. Occasional keratinocytes of the superficial stratum spinosum showed clear cytoplasm vacuoles, or hydropic degeneration; isolated dyskeratotic

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Response to treatment Case

Cephalexin*

Zinc methionin†

Vitamin A alcohol‡

Tretinoin§

Vitamin E¶

Petroleum jelly**

Propylene glycol††

Udder balm‡‡

1 2

No response No response

No response NA

NA No response

No response NA

NA NA

Improved NA

Improved Improved

NA Improved

3 4 5 6 7 8 9

NA NA NA NA NA NA NA

No response NA NA NA NA No response NA



NA NA Improved NA NA NA NA

NA Improved NA NA NA NA NA

No response NA NA Improved No response Improved NA


10 11

NA No response

NA NA

NA NA

NA NA

Improved NA

NA NA

NA NA

NA NA

12

No response

NA

NA

NA

NA

NA

Improved

NA

Comments Needed continuous topical propylene glycol and petroleum jelly to prevent recurrence. After several months of topical propylene glycol, udder balm further improved the lesions, but needs to be applied continuously to prevent recurrence. Needed continuous topical treatment to prevent recurrence. Needed continuous topical treatment to prevent recurrence. Needed continuous topical treatment to prevent recurrence. Needed continuous topical treatment to prevent recurrence. Before examination, had received topical cyclosporin and sunscreens with minimal improvement, as well as oral tetracycline-niacinamide without improvement. No change in hyperkeratotic aspect of the nasal planum lesions following cephalexin, although the mild lesions on the bridge of the nose improved. No change in hyperkeratotic aspect of the nasal planum lesions following cephalexin, although the mild lesions on the bridge of the nose improved. Needed continuous topical treatment to prevent recurrence of lesions on nasal planum.

NA, not administered. *Cephalexin: 22 –30 mg / kg orally BID for 3 – 4 weeks. †Zinc methionin (Pala-Z, Virbac Inc., Forth Worth, TX): 2.5 mg / kg orally once daily or 1.5 mg / kg orally BID for 1 month. ‡Vitamin A alcohol: 20 000 UI orally BID for 1 month. §0.05% tretinoin cream (Retin-A, Janssen-Ortho Inc., Canada): topical applications BID for 1.5 months. ¶Vitamin E: topical applications 1–3 times daily. **Petroleum jelly: topical applications 1–3 times daily. ††67% propylene glycol (Glycol-P, Rhone Merieux Inc., Canada): topical applications 2–3 times daily. ‡‡Udder balm containing hydroxyquinoline sulfate, petrolatum and lanolin (Bag Balm, Dairy Association Co., Rock Island, QC, Canada): applied topically 1–3 times daily.

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Table 1. Response to various treatments for the control of hyperkeratotic nasal dermatitis in Labrador Retrievers

Hereditary nasal parakeratosis cells or cells containing cytoplasmic eosinophilic globular material were also observed. Milder spongiosis was also observed in the stratum basale of 6/10 cases. Mild to moderate exocytosis of neutrophils and lymphocytes was observed in 9/10 cases, the former sometimes present in the spongiotic vesicles, the latter occasionally forming small lymphocytic aggregates. Six of the 10 dogs had evidence of superficial bacterial infection, as indicated by colonies of cocci or foci of dense neutrophil accumulations within the parakeratotic crust. Rare apoptotic cells (< 5 per section) were observed in the stratum basale and spinosum of 7/10 cases. All dogs had mild to moderate sub-basal lymphoplasmacytic infiltration within the superficial dermis, without significant infiltration of the epidermis. In 6/10 cases the inflammatory cells also had a perivascular distribution, localized to the superficial dermis. In all dogs, there was pigmentary incontinence and mild to marked oedema, localized to the tips of the dermal papillae. Other dermal changes included mild to moderate superficial fibrosis, perpendicular to the surface (8/10), and mural fibrosis of superficial blood vessels, confirmed with Masson’s trichrome stain (7/10). Biopsy samples from the milder lesions on the bridge of the nose from two dogs revealed similar histopathological findings. A biopsy from the hyperkeratotic footpad hyperkeratosis of one dog only revealed orthokeratotic hyperkeratosis. Electron microscopy of the epidermis confirmed the spongiosis and presence of exocytosis. In the stratum corneum there were several abnormalities: fibrillarity of the corneocyte cytoplasm, retention of nuclear chromatin, abundant intercellular oedema, and focal intracytoplasmic vacuoles in the cornified cells. In addition, lamellar bodies were not identified at the junction between the stratum granulosum and stratum corneum in the sections examined (Fig. 7). Immunohistochemistry (n = 4) did not reveal significant deposition of IgG in the epidermis or in the

Figure 7. Electron micrograph of the upper nucleated layers and the lower stratum corneum. Hyperkeratotic lesion on nasal planum of a Labrador Retriever. There is marked intercellular oedema defined by granular debris between keratinocytes (E) and elongated intercellular bridges (arrowheads). The two ovoid structures in the upper stratum corneum are neutrophils (N). Note that the lower stratum corneum has numerous intracytoplasmic vacuoles. Lead citrate and uranyl acetate. Bar = 2.5 µm.

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basement membrane zone, and was negative for measles, canine distemper virus antigens and papilloma virus antigens. Fungal cultures (n = 7) and ANA (n = 4) tests were negative. The CBC and biochemistry profiles did not reveal any significant abnormalities. Treatments Different treatments were prescribed in 12 dogs (Table 1).

DISCUSSION The age of onset of this nasal dermatitis in Labrador Retrievers and Labrador Retriever crosses and the familial links between affected dogs are striking features of this condition. Although the latter characteristics are suggestive of an inherited disorder, the exact mode of inheritance remains unknown. As both male and female dogs are affected, a sex-related condition may be ruled out. All sires and dams that produced affected dogs were not clinically affected; we thus speculate at this point that the disease is autosomal recessive.4 Indeed, several canine genetic diseases are believed to be simple Mendelian traits, with ≈ 70% demonstrating autosomal recessive inheritance patterns.5 It is acknowledged that the dissemination of genetic diseases across canine populations is favoured by inbreeding.5 This may have allowed the detection of this new disease and the collection of this series of cases, as inbreeding coefficients in our affected dogs were up to 0.14. The existence of common ancestors between affected dogs suggests that the disease may be due to a unique mutation. However, we did not perform a segregation analysis, to ascertain the mode of inheritance, because we had recorded a limited number of affected dogs, and had limited information regarding affected relatives. A prospective study could be considered in the future to investigate the heritability of the disease. Along with hyperkeratotic parakeratotic lesions of the nasal planum, two dogs had also mild lesions on the haired part of the dorsal nose and one of these also had hyperkeratosis of the footpads. Histopathological findings from the lesions on the bridge of the nose were similar to the results obtained from the nasal planum, suggesting a similar mechanism. However, we do not know if a concurrent footpad hyperkeratosis is a variant of the same disease. Follow-ups were carried out for up to 3 years, and the lesions remained stable, with occasional waxing and waning in the severity of the crusting. The pathogenesis of this new hyperkeratotic parakeratotic nasal dermatitis of Labrador Retrievers remains to be determined. The electron micrographs demonstrated that the cornification process was altered as defined by retention of nuclei, fibrillarity rather than the granular pattern of normal corneocyte cytoplasms, lack of discernable lamellar bodies, and

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abundant intercellular oedema. Moreover, intracellular vacuoles were identified, which may represent lipids that were not secreted intercellularly, perhaps because of oedema or an abnormality in the cornification process. Recent studies report the presence of intracorneal vacuoles in canine skin diseases with parakeratotic hyperkeratosis.6,7 The lipid nature of the vacuoles was determined in congenital follicular parakeratosis. However, the study by Senter et al.7 did not determine whether the vacuoles found in other parakeratotic diseases also contained lipid. The conclusion of this study was that intracorneal vacuoles were a common, nonspecific finding of many parakeratotic skin diseases in the dog. Parakeratosis was a constant histopathological finding in our dogs. It may be the result of an incomplete differentiation, or of a reduced transit time, which does not permit epidermal cells to complete the whole differentiation process. It can also result from direct cellular injury.8 A problem with parakeratotic disorders is that they tend to be associated with inflammation. In humans, for example, psoriasis is characterized by a disturbed differentiation of the epidermal cells resulting in parakeratosis and by an increased epidermal proliferation, leading to acanthosis. The disease is also characterized microscopically by an inflammatory infiltrate in the dermis and epidermis, oedema of the elongated dermal papillae, and changes in the capillaries of the papillary dermis. The stimulus for increased epidermal proliferation is thought to follow signals released from inflammatory leukocytes attracted to the epidermis by the expression of adhesion molecules at the keratinocyte surface.8,9 Whether the lesions in our affected Labrador Retrievers are due to a primary inflammatory disease that affects keratinocyte differentiation or whether a primary cornification disorder stimulates inflammation, is subject to debate. The histopathological changes bear some resemblance to zinc-responsive dermatosis, mucocutaneous pyoderma and actinic keratosis.1,3,10 The parakeratosis retrieved in our histopathological examinations could suggest a vitamin A or a zinc responsive disease.1 However, the fact that three dogs did not respond to zinc supplements does not support a zinc-responsive dermatosis. Parenteral zinc supplementation was not attempted, nor was concomitant treatment with oral prednisone, which could have improved response to zinc therapy due to its antiinflammatory effects on the skin or by improving zinc absorption.2,11 Essential fatty acid supplementation could have also been combined with zinc as it has also been documented to enhance zinc absorption.11 Synthetic retinoids can be useful in the treatment of several cornification disorders in dogs. They regulate proliferation, growth and differentiation of epithelial tissues.1,12,13 Topical tretinoin was of no benefit in one dog. Therapy with oral retinoids was not performed as dog owners declined this treatment due to cost. However, a therapeutic trial with oral retinoids could prove useful in the future. One dog did not respond to a therapeutic trial with oral vitamin A alcohol, but we are

aware of one Labrador Retriever (not included in our study) that was improved with this form of therapy (Dr Emily Rothstein, personal communication). Mucocutaneous pyoderma can present with a lichenoid inflammatory cell infiltrate.1,3 However, the cellular infiltrate is generally more extensive than here and parakeratosis is not a usual finding of this disease. Moreover, four dogs received cephalexin, without improvement of the hyperkeratotic lesions on the nasal planum, although the mild lesions on the hairy part of the bridge of the nose present in two of these dogs improved with this treatment. The histopathological findings in this study also have similarities with actinic keratosis: parakeratotic hyperkeratosis, dermal inflammation and dermal fibrosis.1,10 However, atypia and dysplasia of the epidermis associated with solar-induced keratosis were not found in our cases. Moreover, the nasal lesions started in young dogs, and did not seem to be exacerbated with exposure to sunlight. At this point, the most effective and inexpensive therapy appears to be topical applications of propylene glycol. Emollients such as topical vitamin E or petroleum jelly may also be useful. Other avenues can be explored. For example, 1,25-dihydroxy vitamin D3 (calcitriol) inhibits keratinocyte proliferation and induces terminal differentiation.1,9 It is used in the treatment of psoriasis in humans,9 and has also been administrated to Cocker Spaniels affected with primary idiopathic seborrhoea, with improvement documented in 67% of the dogs.14 Topical or oral use of vitamin D3 analogs could thus be of benefit to Labrador Retrievers with nasal hyperkeratotic dermatitis. However, because these medications influence calcium metabolism and accidental overdosing can be fatal, the patient should have its PTH, calcium, and phosphorus levels closely monitored.1 Since these cases have been documented, the authors have heard of ≈ 20 additional cases in Québec. In addition, we recently made an inquiry on an Internet veterinary dermatology list-serv to evaluate the worldwide occurrence of this disorder and its clinical variants. Labrador Retrievers with clinicopathological findings compatible with the disorder reported here have been seen in several countries (USA, UK, Belgium, Australia, New Zealand). Most of these dogs had lesions restricted to the nasal planum, but a few had also lesions elsewhere: the hairy part of the bridge of the nose, the footpads and around pinnal margins. It is likely that this disorder has been present in Labrador Retrievers for some time but was not recognized as a genetically determined disorder. Owing to the popularity of this breed, the spreading of the genetic defect and the new recognition of this disorder, it is likely that it will be diagnosed more frequently in the future. In conclusion, hyperkeratotic parakeratotic nasal dermatitis is a clinically manageable but incurable dermatosis of early onset and variable severity in Labrador Retrievers. No apparent sex or coat colour predilections appear to exist. The striking breed


Hereditary nasal parakeratosis predilection and the early age of onset suggest that it is a genodermatosis, with the transmission most likely autosomal recessive. From now on, this entity should be on the differential diagnosis when compatible clinical history and lesions are seen in Labrador Retrievers or Labrador Retriever crosses.

ACKNOWLEDGEMENTS This study was funded by the ‘Académie de médecine vétérinaire du Québec’. The authors would like to acknowledge Dr Caroline de Jaham, for management of one case, Dr Alain Ducos, for genetic counseling, Drs Allan Bell, Sonya Bettenay, Jan Declercq, Jacques Fontaine, Peter Ihrke, Diane Lewis, Ken Mason, Emily Rothstein, David Senter, David Shearer and Roger Wilkinson for sharing case information with us, and the breeders and owners of the dogs for their cooperation. Reprints will not be available from the authors. REFERENCES 1. Scott, D.W., Miller, W.H., Griffin, C.E. Small Animal Dermatology, 6th edn. Philadelphia: W.B. Saunders, 2000. 2. Kwochka, K.W. Primary keratinization disorders of dogs. In: Griffin, C.E, Kwochka, K.W., Macdonald, J.M., eds. Current Veterinary Dermatology, the Science and Art of Therapy. St. Louis, MO: Mosby Year Book, 1993: 176 – 90. 3. Yager, J.A., Wilcock, B.P. Color Atlas and Text of Surgical Pathology of the Dog and Cat, Dermatopathology and Skin Tumors, Vol. 1. London: Wolfe Publishing, 1994.

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4. Nicholas, F.W. Introduction to Veterinary Genetics. New York: Oxford University Press 1996, 154–61. 5. Brooks, M., Sargan, D.R. Genetic aspects of disease in dogs. In: Ruvinsky, A., Sampson, J., eds. The Genetics of the Dog. Wallingford, UK: CABI Publishing, 2001: 191–266. 6. Lewis, D.T., Messinger, L.M., Ginn, P.E. Multiple congenital defects in five rottweiler dogs. Veterinary Dermatology 1998; 9: 61–2. 7. Senter, D.A., Scott, D.W., Miller, J.R. et al. Intracorneal vacuoles in skin diseases with parakeratotic hyperkeratosis in the dog. a retrospective light-microscopy study of 111 cases (1973–2000). Veterinary Dermatology 2002; 13: 43–7. 8. Wolff, K., Kibbi, A.-G., Mihm, M.C. Jr. Basic pathologic reactions of the skin. In: Freedberg, I.M. et al., eds. Fitzpatrick’s Dermatology in General Medicine, 5th edn. San Francisco: McGraw-Hill, 1999: 41–55. 9. Christophers, E., Mrowietz, U. Psoriasis. In: Freedberg, I.M. et al., eds. Fitzpatrick’s Dermatology in General Medicine, 5th edn. San Francisco: McGraw-Hill, 1999: 495–520. 10. Gross, T.L., Ihrke, P.J., Walder, E.J. Veterinary Dermatopathology. A Macroscopic and Microscopic Evaluation of Canine and Feline Skin Diseases. St. Louis, MO: Mosby Year Book, 1992: 155–6. 11. Colombini, S. Canine zinc-responsive dermatosis. Veterinary Clinics of North America: Small Animal Practice 1999; 29: 1373–83. 12. Kwochka, K.W. Retinoids and vitamin A. therapy. In: Griffin, C.E., Kwochka, K.W., Macdonald, J.M., eds. Current Veterinary Dermatology, the Science and Art of Therapy. St. Louis, MO: Mosby Year Book, 1993: 203–10. 13. Power, H.T., Ihrke, P.J. The use of synthetic retinoids in veterinary medicine. In: Bonagura, J.D., ed. Kirk’s Current Veterinary Therapy XII. Philadelphia: W.B. Saunders, 1995: 585–90. 14. Kwochka, K.W. Advances in the management of canine scaling. Proceedings of the Third World Congress of Veterinary Dermatolology Edinburgh, 1996: 99–101.

Résumé Une dermatite nasale héréditaire est rapportée chez 14 Labrador retrievers et 4 croisés Labrador retriever. Il semble qu’il s’agisse d’une nouvelle génodermatose, pour laquelle un mode de transmission autosomal récessif est suspecté. Les lésions apparaissent entre 6 et 12 mois d’âge. L’examen histopathologique montre une hyperkératose parakératosique, souvent associée à une accumulation multifocale d’un fluide protéique entre les kératinocytes de la couche cornée et de la couche épineuse. Une infiltration lymphoplasmocytaire sous-basale a été observée dans le derme superficiel. Les marquages immunohistochimiques étaient négtaifs pour les IgG (n=4), le virus de la maladie de Carré et les papillomavirus (n=4). Le dosage des ANA sériques était également négatif (n=4) ainsi que la culture fongique (n=7). La microscopie électronique a révélé une anomalie du processus de cornification: rétention de la chromatine nucléaire, absence de corps lamellaires et œdème intercellulaire marqué. Les chiens n’ont pas répondu à l’administration orale de zinc méthionine (n=3), de céphalexine (n=4), de vitamine A (n=1) ou à l’application topique de trétinoïne (n=1). Une amélioration des lésions a été obtenue avec l’application locale de vitamine E (n=2), de pétrole (n=2), et de propylene glycol (n=5). Resumen Se documenta una dermatitis nasal hereditaria en 14 Labrador retrievers y en 4 cruces de Labrador retriever. Parece ser una nueva alteración hereditaria para la cual se sospecha un modo de herencia autosómico recesivo. Las lesiones fueron observadas por primera vez entre los 6 y 12 meses de edad. En los análisis histopatológicos se observó una hiperqueratosis paraqueratótica, a menudo con una acumulación marcada de fluido proteínaceo entre los queratinocitos de los estratos córneo y espinoso superficiales. También existía una infiltración linfoplasmacítica sub-basal en la dermis superficial. Las tinciones immunocitoquímicas para IgG (n=4), virus del moquillo y papilomavirus (n=4) fueron negativas, así como la determinación de ANA séricos (n=4) y cultivos fúngicos (n=7). Mediante microscopía electrónica se observó un proceso de cornificación alterado: retención de cromatina nuclear, ausencia de cuerpos lamelares y edema intercelular marcado. Los perros no respondieron a la administración oral de metionina de zinc (n=3), cefalexina (n=4), alcohol de vitamina A (n=1) o tretinoina tópica (n=1). Se obtuvo una mejora de las lesiones con tratamiento tópico de vitamina E (n=2), gelatina de petróleo (n=2) y glicol de propileno (n=5). © 2003 European Society of Veterinary Dermatology Ltd, Veterinary Dermatology, 14, 103–110

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N. Pagé et al. Zusammenfassung Hereditäre nasale Dermatitis wird bei 14 Labrador Retrievern und 4 Labrador Retrievermischlingen beschrieben. Dies scheint eine neubeschriebene erbliche Erkrankung zu sein, für die ein autosomaler rezessiver Erbgang vermutet wird. Die Läsionen wurden zuerst im Alter von 6 bis 12 Monaten bemerkt. Histopathologische Analyse ergab parakeratotische Hyperkeratose, oft mit ausgeprägter Anreicherung von proteinartiger Flüssigkeit zwischen Keratinozyten innerhalb des Stratum corneums und oberflächlichen Stratum granulosums. Eine subbasiläre lymphozytische Infiltration wurde innerhalb der oberflächlichen Dermis gesehen. Immunhistochemische Färbung auf IgG (n=4), Staupe und Papillomaviren (n=4) waren genauso negativ wie Serum ANA (n=4) und Pilzkultur (n=7). Elektronenmikroskopie ergab einen abnormalen Kornifikationsprozess: Retention von nuklearem Chromatin, Anwesenheit von Lamellarkörpern und ausgeprägtes interzelluläres Ödem. Hunde sprachen nicht auf die orale Gabe von Zinkmethionin (n=3), Cephalexin (n=4), Retinol (n=1) oder lokalem Tretinoin (n=1) an. Besserung der Läsionen wurde mit lokalem Vitamin E (n=2), Vaseline (n=2), und Propylenglykol (n=5) erreicht.
