Hyperkeratotic erythema multiforme variant in 17 dogs.

BACKGROUND: A new canine subgroup defined as 'old-dog' or 'hyperkeratotic' erythema multiforme (HKEM) with marked hyperkeratosis and parakeratosis has been proposed without any detailed description of larger case series. OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, and histopathological and immunological findings in 17 dogs with HKEM. ANIMALS: Inclusion criteria were the presence of (i) scaly skin lesions with or without crusting; and (ii) microscopic lesions typical of EM (i.e. a panepidermal cytotoxic lymphocytic dermatitis with or without basal keratinocyte apoptosis); and (iii) microscopic ortho- and/or parakeratotic hyperkeratosis affecting the interfollicular epidermis. MATERIALS AND METHODS: Clinical questionnaires and skin biopsies were reviewed. Polymerase chain reactions for epidermotropic viruses and direct immunofluorescence were performed. RESULTS: Various breeds were affected with an over-representation of males in their mid-to-late adulthood (median age 9 years). Generalised skin lesions included multifocal-to-coalescing, linear and annular macules and plaques with erythema and adherent firm crusting. Microscopic lesions were specific for EM and featured prominent superficial epidermal apoptosis with lymphocytic satellitosis and parakeratosis. No drug triggers were identified. Polymerase chain reactions for canine herpesvirus polymerase gene, canine parvovirus and canine distemper virus were negative in all HKEM and canine erosive EM (15 dogs) biopsies. Lesions failed to respond to oral and/or topical antimicrobials. Complete remission of signs was achieved in 9 of 17 dogs (53%) using immunosuppressive regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperkeratotic erythema multiforme (HKEM) is a chronic, persistent and clinically distinctive erythema multiforme (EM) variant that differs from 'classic' vesiculobullous erosive-to-ulcerative EM in dogs.

Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK).

Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in the SUV39H2 gene encoding a histone 3 methyltransferase involved in epigenetic silencing. Formalin-fixed biopsies of the nasal planum of Labrador Retrievers were screened by immunofluorescence microscopy for the presence and distribution of epidermal proliferation and differentiation markers. Gene expression of these markers was further analysed using RNA sequencing (RNA-seq) and ultrastructural epidermal differences were investigated by electron microscopy. Differentiation of the nasal planum in the basal and suprabasal epidermal layers of HNPK-affected dogs (n = 6) was similar compared to control dogs (n = 6). In the upper epidermal layers, clear modifications were noticed. Loricrin protein was absent in HNPK-affected nasal planum sections in contrast to sections of the same location of control dogs. However, loricrin was present in the epidermis of paw pads and abdominal skin from HNPK dogs and healthy control dogs. The patterns of keratins K1, K10 and K14, were not markedly altered in the nasal planum of HNPK-affected dogs while the expression of the terminal differentiation marker involucrin appeared less regular. Based on RNA-seq, LOR and IVL expression levels were significantly decreased, while KRT1, KRT10 and KRT14 levels were up-regulated (log2fold-changes of 2.67, 3.19 and 1.71, respectively) in HNPK-affected nasal planum (n = 3) compared to control dogs (n = 3). Electron microscopical analysis revealed structural alterations in keratinocytes and stratum corneum, and disrupted keratinocyte adhesions and distended intercellular spaces in lesional samples (n = 3) compared to a sample of a healthy control dog (n = 1). Our findings demonstrate aberrant keratinocyte terminal differentiation of the nasal planum of HNPK-affected Labrador Retrievers and provide insights into biological consequences of this inactive SUV39H2 gene variant.

Effect of dietary neutral detergent fibre source on lambs growth, meat quality and biohydrogenation intermediates.

With this trial we have tested the effects of structural and chemical composition of neutral detergent fibre (NDF) of the diet on lamb fatty acid composition of meat and subcutaneous fat. Twenty lambs, were fed complete diets with low starch and similar NDF content of different origin (ground alfalfa or soybean hulls). Animal performance and product quality were not affected by treatments. Rumen pH increased and parakeratosis intensity decreased with the level of alfalfa in the diet. Increasing the alfalfa proportion in the diet decreased t10-18:1 (P = .023), increased t11-18:1 (P = .003) and decreased the t10/t11 ratio according to a quadratic pattern (P = .020). Chemical composition and structure of the diet's fibrous fraction influenced the BI pattern of the final product. Forty percent of alfalfa in diet reduced the severity of t10-shift, but for its full resolution, other factors should be considered including forage particle size and buffering capacity of the diet.

A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis.

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5'-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5'-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.

Localized parakeratotic hyperkeratosis in sixteen Boston terrier dogs.

BACKGROUND: Although zinc responsive dermatosis is typically a disorder of Arctic breed dogs, this study identifies similar cutaneous lesions on the face and pressure points of Boston terrier dogs. HYPOTHESIS/OBJECTIVES: To document the clinical and histological features of localized parakeratotic hyperkeratosis of Boston terrier dogs, to determine if the lesions respond to zinc supplementation and to determine whether tissue zinc levels were decreased in affected versus unaffected dogs. MATERIAL AND METHODS: Sixteen Boston terrier dogs with similar gross and histological findings were identified retrospectively from two institutions. Follow-up information for nine dogs from one institution was obtained from referring veterinarians using a questionnaire. Tissue zinc levels were measured from formalin-fixed paraffin-embedded skin biopsy samples of affected and unaffected dogs using inductively coupled plasma mass spectrometry. RESULTS: Mild to severe parakeratotic hyperkeratosis with follicular involvement was present in all 16 cases. Of the nine dogs for which follow-up information was available, five dogs received oral zinc supplementation and four dogs had documented clinical improvement or resolution of dermatological lesions. The median skin zinc levels were not significantly different between affected and unaffected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge this is the first report of localized parakeratotic hyperkeratosis in Boston terrier dogs, some of which improved with oral zinc supplementation. Prospective studies in Boston terrier dogs are warranted to document potential zinc deficiency (serum and/or tissue levels, pre- and post-treatment) and to objectively assess response to zinc supplementation and other therapies.

Diet and diet-related disorders in captive ruminants at the national zoological gardens of South Africa.

Although diet-related disorders have received much attention in the zoo literature, evidence-based results on relationships between diet and disease are still rare, often due to a lack of quantitative dietary information that can be linked to clinical or necropsy reports. We investigated 24 species of captive ruminants from one facility for which quantitative feeding instructions and necropsy reports between 1991 and 2012 were available. Species were classified as grazer (GR), intermediate feeder (IM), or browser (BR). Feeding type and body mass were significantly correlated to the diet fed, with smaller and BR species receiving higher proportions of non-roughage diet items. There were no significant differences between feeding types in the occurrence of parakeratosis/ruminitis/acidosis (PRA) at necropsy, but in body condition score, with BR more often in poor and less often in excellent body condition at necropsy. While there was no direct correlation between the proportion of non-roughage diet items and PRA across species, there was a significant effect of the proportion of non-roughage diet items on PRA when body mass was also taken into account: larger species, and those that received more non-roughage diet items, had higher prevalence of PRA. The results underline that diet and lack of structured feed items can be associated with the disease complex of acidosis in ruminants, but also suggest that this is modified by factors related to animal size. These latter may include susceptibility to acidosis, or husbandry-related opportunities to monopolize non-roughage feeds and ingest higher proportions than intended by feeding instructions.

History of zinc in agriculture.

Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application.

Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy cow: a case report.

A mature dairy cow was transitioned from a high forage (100% forage) to a high-grain (79% grain) diet over seven days. Continuous ruminal pH recordings were utilized to diagnose the severity of ruminal acidosis. Additionally, blood and rumen papillae biopsies were collected to describe the structural and functional adaptations of the rumen epithelium. On the final day of the grain challenge, the daily mean ruminal pH was 5.41+/-0.09 with a minimum of 4.89 and a maximum of 6.31. Ruminal pH was under 5.0 for 130 minutes (2.17 hours) which is characterized as the acute form of ruminal acidosis in cattle. The grain challenge increased blood beta-hydroxybutyrate by 1.8 times and rumen papillae mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase by 1.6 times. Ultrastructural and histological adaptations of the rumen epithelium were imaged by scanning electron and light microscopy. Rumen papillae from the high grain diet displayed extensive sloughing of the stratum corneum and compromised cell adhesion as large gaps were apparent between cells throughout the strata. This case report represents a rare documentation of how the rumen epithelium alters its function and structure during the initial stage of acute acidosis.

Hereditary nasal parakeratosis in Labrador retrievers: 11 new cases and a retrospective study on the presence of accumulations of serum ('serum lakes') in the epidermis of parakeratotic dermatoses and inflamed nasal plana of dogs.

We report 11 new cases of hereditary nasal parakeratosis in Labrador retrievers. The disease was first observed when the dogs were 6 months to 2 years of age, and affected dogs of either sex and all coat colours. Hyperkeratosis and depigmentation were confined to the nasal planum, and affected dogs were otherwise healthy. The principal histological findings in biopsy specimens were marked diffuse parakeratotic hyperkeratosis, multiple intracorneal serum lakes and superficial interstitial-to-interface lymphoplasmacytic dermatitis. Topical applications of propylene glycol in water or white petrolatum were often effective for treatment of the dermatosis. However, continued applications were required to maintain a beneficial response. A retrospective histological study of parakeratotic inflammatory diseases of canine haired skin and inflammatory diseases of the canine nasal planum was performed. The degree of parakeratotic hyperkeratosis and the number and size of intracorneal serum lakes were evaluated. The degree of parakeratotic hyperkeratosis was greater in hereditary nasal parakeratosis specimens than that seen in discoid lupus erythematosus and Malassezia dermatitis. There were more serum lakes in hereditary nasal parakeratosis specimens than in specimens from dogs with discoid lupus erythematosus, Malassezia dermatitis, primary seborrheic dermatitis or zinc-responsive dermatosis. Significant differences in sizes of serum lakes (if present) were not seen.

Hereditary nasal parakeratosis in Labrador Retrievers.

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).

Citrus pulp for cattle.

Citrus pulp is classified as an energy concentrate by-product feed. Citrus by-products fed to beef cattle include citrus molasses, citrus meal, wet citrus pulp, dried citrus pulp, and pelleted citrus pulp; however, in current production systems, pulp (wet, dry, and pelleted) is the only by-product commonly used. Citrus pulp production in the United States is limited to specific subtropical regions, of which south central Florida remains the largest with additional production in California and Texas.

Intracorneal vacuoles in skin diseases with parakeratotic hyperkeratosis in the dog: a retrospective light-microscopy study of 111 cases (1973-2000).

Two recent case reports described a congenital keratinization defect (congenital follicular parakeratosis; CFP) in Rottweiler and Siberian Husky dogs. Skin biopsy specimens revealed marked parakeratosis targeting the hair follicle and numerous intracorneal vacuoles. A retrospective histopathological study was conducted on skin biopsy specimens from 111 dogs with diseases associated with parakeratotic hyperkeratosis to determine whether intracorneal vacuoles were present. Additional criteria evaluated were the size and location of the vacuoles and the degree of parakeratosis. Cases examined included dogs with primary idiopathic seborrhoea, necrolytic migratory erythema (NME), Malassezia dermatitis, zinc-responsive dermatosis, hereditary nasal hyperkeratosis of Labrador Retriever dogs, thallotoxicosis and CFP. Thirty-seven cases (37/111, 33%) had intracorneal vacuoles, including nine cases of primary idiopathic seborrhoea (9/29, 31%), 10 cases of NME (10/18, 56%), five cases of Malassezia dermatitis (5/19, 26%), five cases of zinc-responsive dermatosis (5/36, 14%), five cases of hereditary nasal hyperkeratosis (5/5, 100%) and three cases of CFP (3/3, 100%). If present, intracorneal vacuoles were found throughout all layers of the parakeratin. The sizes of intracorneal vacuoles varied among diseases, but large (> 5 microm) vacuoles only were present in CFP. Biopsies with a larger degree of parakeratosis were significantly more likely to have intracorneal vacuoles (P = < 0.001). Based on this study, intracorneal vacuoles are a common finding in many parakeratotic skin diseases of the dog, but large (> 5 microm) vacuoles are found only in CFP.

Methods for exposure of laboratory animals to ultraviolet radiation.

Two different sources of ultraviolet B (UVB) radiation, an electronically controlled UVB exposure unit, containing FS40 tubes, and a hand-held Kromayer lamp, were evaluated for actual irradiance in W/m2 and spectra (physical dosimetry and biological dosimetry (skin effects in rodents)). The technical studies of the FS40 sources demonstrated that the flux intensity of the lamps could be changed electronically, without affecting the spectrum. Thus it was possible to standardize UVB exposure electronically. The biologically effective doses of these sources were analysed in RIV-Tox Wistar rats and BALB/c mice. After low doses of UVB radiation, histopathological changes such as acanthosis, hyperkeratosis and dermal inflammation were observed in the skin without the presence of major side effects such as erythema and oedema. After higher doses of UVB radiation erythema and oedema were clearly visible. Quantitative studies showed that the minimal erythema dose, as a biological parameter, correlated well to the emission in J/m2. In addition, biological parameters such as acanthosis and inflammation in the skin correlated well to the actual exposure in J/m2 and were sensitive biomarkers for UVB-induced skin toxicity. Thus, in addition to minimal erythemal doses, acanthosis and inflammation may also be applied as biologically relevant doses for studies of the biological effects of UVB radiation.

Development and evaluation of an endoscopic technique permitting rapid visualization of the cardiac region of the porcine stomach.

Our study was designed to ascertain whether a flexible videoscope could be used to efficiently monitor ulcers of the pars esophagea in a large group of grower-finisher swine. Gastroscopy was performed on 2 separate occasions in 32 pigs following anesthesia with intravenous pentobarbital, and ulcers of the pars esophagea were subjectively graded. The pigs were then necropsied. Grades from the second endoscopic examination were compared for agreement with grades derived from gross inspection of the pars esophagea at necropsy, and with grades derived from histopathologic examination of sections of the same region. The pars esophagea was adequately visualized in all endoscopic examinations. The average duration of each examination, from anesthetic induction, was approximately 8 min. Gastroscopy permitted appreciation of a wide range of focal and diffuse superficial and deep ulcerative lesions of the pars esophagea, but failed to unequivocally identify parakeratosis of the pars esophagea. Agreement between endoscopic and subsequent necroscopic and histopathologic gradings of ulcerations was poor. We concluded that the use of a flexible videoscope permitted rapid inspection of the pars esophagea, and was therefore a practical method of experimentally monitoring the progression of spontaneous gastric ulcers in pigs. We also postulated that the poor agreement between endoscopic and postmortem findings occurred because endoscopy was possibly more sensitive at detecting small and superficial ulcerations. However, further studies are needed to verify the accuracy of endoscopic diagnosis of gastric ulcers in the live pig.

[Symptoms and course of a parakeratosis outbreak in a boar raising facility]. / Symptomatik und Verlauf eines Parakeratose-Ausbruchs in einem Eberaufzuchtbetrieb.

A case of parakeratosis in pigs due to secondary zinc deficiency (zinc/calcium ratio 0.4 g/100 g; 68.7 mg zinc, 17.1 g calcium per kg food) is reported. Morbidity and symptoms were much more marked in growing boars than in female animals of the same age. In sows the disorder appeared ten days after the first symptoms were seen in the boars. Adult breeding pigs developed no signs of parakeratosis.

Dietary fibre in the diet of the growing pig: effects on apparent digestibility and resultant implications for its use in reducing the incidence of oesophagogastric parakeratosis.

The effects on apparent digestibility of increasing dietary fibre concentrations in barley-based diets by substituting for barley either bran, oatmeal by-product, guar gum or pectin were studied using 72 pigs. Increasing substitutions of bran up to a maximum of 300 g kg-1 gave progressive decreases in apparent digestibility of dry matter, ether extract and gross energy fractions and in digestible and metabolisable energy contents, progressive increases in apparent digestibility of modified acid detergent fibre but had no consistent effect on either nitrogen or extract free of nitrogen fractions. Increasing substitution of oatmeal by-product up to the same maximum gave significant linear decreases in apparent digestibility of dry matter, extract free of nitrogen and gross energy, significant depressions in apparent digestibility of modified acid detergent fibre and significant increases in ether extract. Guar gum and pectin, both substituted to a maximum of 50 g kg-1 had no significant effects on apparent digestibility. The results are discussed in the context of the concentrations of dietary fibre needed to reduce the incidence of oesophagogastric parakeratosis.

Histopathological development of equine cutaneous papillomas.

The histopathological development of equine cutaneous papillomas was studied in 78 warts naturally occurring in 50 one to 3-year-old Thoroughbred or Arab horses and in 54 warts experimentally induced in three 2-year-old Thoroughbreds. Lesions in the natural cases were categorized into three phases, growth, development and regression. Main lesions of the growing phase were marked hyperplasia of the basal cells and mild to moderate acanthosis, hyper- and parakeratosis with a few intranuclear inclusion bodies (IIB) which were positive with anti-bovine papillomavirus serum. In the developing phase, there was prominent acanthosis with cellular swelling and fusion, and marked hyper- and parakeratosis. Many IIB were also present in swollen or degenerative prickle cells and granular cells, with a high degree of parakeratosis in keratinocytes. In the regressing phase, epidermal layers were almost normal with only slight hyperplastic change. However, there was rete peg proliferation downward into the dermis with moderate proliferation of fibroblasts and collagen fibres. In addition, in 10 spontaneous and one experimental wart, the lesions were fibropapillomas and this has never been described in horses previously. It was concluded that papillomas were initiated by basal cell hyperplasia without viral antigen production, with formation of acanthosis and hyper- and parakeratosis with IIB production. These findings were confirmed by examination of the experimental cases on the basis of the gross diameter of the warts.

Naltrexone for treatment of acral lick dermatitis in dogs.

Acral lick dermatitis (lick granuloma) was diagnosed in 11 dogs on the basis of history, physical examination, and histopathologic findings. A predilection for the left forelimb was noticed. All 11 dogs were given the narcotic antagonist naltrexone. Successful treatment (cessation of licking, reepithelialization of lesions) was seen in 7 dogs. All 7 dogs' lesions recurred when naltrexone was stopped, but reepithelialized in 5 dogs when the drug was readministered. Adverse effects (drowsiness, withdrawal from owner) were seen in 1 dog, but resolved within 48 hours of stopping the drug.

[Hair alterations in trichophytosis of roe deer--a differential diagnosis for hair parakeratosis]. / Haarveränderungen bei der Trichophytie des Rehwildes--eine Differentialdiagnose zur Haarparakeratose.

A rare case of mycosis (ringworm) in a female roedeer is described and compared with parakeratosis of hair. It seems that in game, parakeratosis--as a primary lesion--predisposes to mycosis.