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.     

Subepidermal linear alignment of mast cells in inflammatory dermatoses of the dog

A recent study demonstrated that 47.7% of dogs with Malassezia dermatitis had a subepidermal linear alignment of mast cells (SLAM). A retrospective histopathological study was conducted on 419 canine skin biopsies to determine if a SLAM was present in other inflammatory diseases. Cases examined included dogs with demodicosis, sarcoptic mange, dermatophytosis, pemphigus foliaceus, pemphigus erythematosus, discoid lupus erythematosus, systemic lupus erythematosus, erythema multiforme, dermatomyositis, staphylococcal pyoderma, primary seborrhea, arthropod bites, contact hypersensitivity, flea bite hypersensitivity, atopy, and food hypersensitivity. Three cases (3/419, 0.7%) were identified with SLAM. The diagnoses for these cases were atopy (1/23, 4%) with a secondary bacterial folliculitis (1/136, 0.7%), pemphigus erythematosus (1/18, 6%), and discoid lupus erythematosus (1/16, 6%). Based on this study, SLAM is significantly more common in Malassezia dermatitis than in other inflammatory diseases.     

Canine discoid lupus erythematosus

Two dogs were found to have clinical, histopathological and immunofluorescent findings compatible with a diagnosis of canine discoid lupus erythematosus. The primary lesions included erythema and depigmentation of the nasal planum. Both dogs responded favorably to systemic corticosteroid therapy.     

A retrospective study comparing the histopathological features and response to treatment in two canine nasal dermatoses, DLE and MCP

Canine discoid lupus erythematosus (DLE) and mucocutaneous pyoderma (MCP) have overlapping clinical and histopathological changes, often making diagnosis difficult. Histopathological features of 27 nasal planum biopsies were scored to determine whether DLE and MCP were histopathologically distinguishable. Long-term follow-up, enabling assessment of clinical diagnoses, was available on 15 cases; 11/15 cases were immunomodulatory responsive (ImR) and 4/15 were antibiotic responsive (AbR). Clinical diagnosis, determined by response to treatment for 15/27 cases, was not predictable based on scoring of histopathological features. Distinct histopathological patterns were observed: 2/11 ImR cases had a lymphocyte-rich interface dermatitis. All other cases had the same histopathological changes: a band-like diffuse superficial plasmacytic to lymphoplasmacytic dermatitis +/- focal basal cell damage, but different clinical diagnoses (4/4 AbR, 9/11 ImR). German shepherd dogs/crosses were over-represented (44.4% of the cases) and tended to have more multifocal lesions (41.7% vs. 26.7% of all other breeds). Longer duration of disease was associated with a preponderance of plasmacytic infiltrate (P = 0.026).     

Malassezia dermatitis in the dog: a retrospective histopathological and immunopathological study of 86 cases (1990–95)

A retrospective histopathological and immunopathological study was conducted on 86 dogs with Malassezia dermatitis. West Highland White terriers, English Setters, Shih Tzus, Basset Hounds, American Cocker Spaniels, spayed females, and castrated males were found to be at increased risk. The histopathological reaction pattern of lymphocytic superficial perivascular to interstitial dermatitis with parakeratotic hyperkeratosis, irregular epidermal hyperplasia, diffuse intercellular oedema and lymphocytic exocytosis was found to be consistent with a diagnosis of Malassezia dermatitis whether yeast were histologically visible (73.3% of the cases) or not (26.7%). Immunopathological studies revealed that 60– > 90% of the inflammatory cells within the epidermis, and 25–75% of those within the dermis were CD3+T lymphocytes, and that the only immunoglobulin-positive cells were dermal plasma cells.     

Antibiotic responsive ulcerative dermatoses in German Shepherd Dogs with mucocutaneous pyoderma

Mucocutaneous pyoderma is a disease of unknown aetiology affecting mucocutaneous skin and is responsive to antibacterial therapy. It is reported to affect the lips, nasal planum, nares, perioral skin and less commonly, the eyelids, vulva, prepuce and anus. Three cases of mucocutaneous pyoderma are presented. Two of the cases showed ulcerative lesions in the inguinal and axillary regions in addition to more typically reported lesions. Two of the dogs had concurrent atopic dermatitis and the third had clinical signs suggestive of hyper-sensitivity disease. The clinical and histopathological features, differentiation of mucocutaneous pyoderma from discoid lupus erythematosus, and long-term management of mucocutaneous pyoderma are discussed.     

Serum antibodies to Malassezia yeasts in canine atopic dermatitis

Significant numbers of humans with atopic dermatitis develop Malassezia-specific IgE. Immediate skin-test reactivity to Malassezia has been demonstrated in atopic dogs. The aim of this study was to compare the serum IgG and IgE response to Malassezia in atopic dogs with and without clinical evidence of Malassezia dermatitis and/or otitis, nonatopic dogs with clinical evidence of Malassezia dermatitis and/or otitis and healthy dogs. Cytology was used to diagnose clinically significant Malassezia dermatitis and otitis. Contact plate cultures confirmed the validity of this technique. Reproducible enzyme-linked immunosorbent assays for Malassezia-specific IgG and IgE in canine serum were established. Atopic dogs had significantly higher serum IgG and IgE levels than either healthy dogs or nonatopic dogs with clinical evidence of Malassezia dermatitis and/or otitis. There was no significant difference in IgG and IgE levels between atopic dogs with and without clinical evidence of Malassezia dermatitis and/or otitis. The implications of these findings in the pathogenesis and management of canine atopic dermatitis are discussed.     

Primary seborrhoea in English springer spaniels: A retrospective study of 14 cases

Primary seborrhoea was diagnosed in 14 English springer spaniels over a 17-year period. Seven of the dogs developed clinical signs by two years of age. The dermatosis began as a generalised non-pmritic dry scaling which gradually worsened. Some dogs remained in this dry (seborrhoea sicca) stage, but in most cases the dermatosis became greasy and inflamed (seborrhoea oleosa and seborrhoeic dermatitis). Eight of the dogs suffered from recurrent episodes of superficial or deep bacterial pyoderma. Histological findings in skin biopsy specimens included marked orthokeratotic hyperkeratosis of surface and infundibular epithelium, papillomatosis, parakeratotic capping of the papillae, and superficial perivascular dermatitis in which lymphocytes and mast cells were prominent. The dogs with seborrhoea sicca responded more satisfactorily to therapy with topical emollient-humectant agents or oral omega-3/omega-6 fatty acid supplementation. Dogs with seborrhoea oleosa and seborrhoeic dermatitis did not respond satisfactorily to topical therapy. One dog, however, responded well to etretinate and omega-3/omega-6 fatty acid administration. No dog was cured.     

Investigation of antibodies to extractable nuclear antigens in dogs.

Determination of antibodies to specific nuclear antigens, termed extractable nuclear antigen (ENA), was investigated in healthy dogs and in dogs with autoimmune, inflammatory, and neoplastic diseases. Using a counterimmunoelectrophoresis method, the dogs' sera were tested for antibodies against the nuclear antigens single-stranded DNA, Sm, Ro, La, ribonucleoprotein, Scl, and proliferating cell nuclear antigen. Antibodies to the Ro antigen were found in 1 dog with discoid lupus erythematosus, in 1 dog with pemphigus erythematosus, and in 1 dog with facial pyoderma and chronic superficial keratitis. In 15 dogs, antibodies were detected to ENA, but the precipitin lines were too weak to identify the specific ENA. These antibodies were found in some dogs with systemic lupus erythematosus, discoid lupus erythematosus, pemphigus erythematosus, dermatomyositis, vitiligo, lymphoma; in the dog with facial pyoderma and chronic superficial keratitis; and in 1 healthy dog. The highest percentage of dogs with antibodies to ENA in a large series (greater than 8) of this study was in dogs with systemic lupus erythematosus (4 of 13; 31%).     

The prevalence of apoptotic keratinocytes in equine epidermis: a retrospective light-microscopic study of skin-biopsy specimens from 253 horses with normal skin or inflammatory dermatoses

A retrospective study was performed to assess the prevalence of apoptotic epidermal keratinocytes in biopsy specimens from 226 horses with inflammatory dermatoses and from 27 normal specimens. One or more apoptotic keratinocytes were found in specimens from 28 of 226 (12%) horses with various dermatoses, and in one of 27 (4%) specimens from normal horses. The prevalence (proportion of cases with apoptotic epidermal keratinocytes) of apoptotic keratinocytes in the group composed of discoid lupus erythematosus, erythema multiforme, photodermatitis, and systemic lupus erythematosus was significantly greater (52% prevalence in these cases) than that in a grouping of all other dermatoses (prevalence 8%). There was no correlation between the number of apoptotic keratinocytes and the extent of epidermal hyperplasia or hyperkeratosis.     

Clinical, histopathological and immunological characteristics of exfoliative cutaneous lupus erythematosus in 25 German short-haired pointers

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, were characterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hereditary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lameness affected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinical phenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG antibodies were demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease usually responds poorly to immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatory therapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This study demonstrates the existence of a cellular and humoral immune response directed against the epidermal basement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to further characterize the immunological pathogenesis of this disease.     

Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus

OBJECTIVE: To evaluate the effect of long-term treatment with tetracycline and niacinamide on antibody production in dogs by measuring postvaccinal serum concentrations of antibodies against canine parvovirus and canine distemper virus. ANIMALS: 10 dogs receiving long-term treatment with tetracycline and niacinamide (treatment group) and 10 healthy dogs (control group). PROCEDURE: The treatment group included 9 dogs with discoid lupus erythematosus and 1 dog with pemphigus foliaceus on long-term treatment (> 12 months) with tetracycline and niacinamide. The control group included 10 healthy dogs with no clinical signs of disease and no administered medications for the past 3 months. Blood samples were obtained from all dogs by jugular venipuncture. Serum antibody titers against canine parvovirus and canine distemper virus antigens were measured, using hemaglutination inhibition and serum neutralization, respectively, and compared between groups. RESULTS: A significant difference in antibody titers between treatment- and control-group dogs was not found. All dogs had protective antibody titers against canine distemper virus, and 8 of 10 dogs from each group had protective titers against canine parvovirus infection. CONCLUSION AND CLINICAL RELEVANCE: These results provide evidence that long-term treatment with tetracycline and niacinamide does not interfere with routine vaccinations and thus does not seem to influence antibody production in dogs.     

Use of tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs.

A combination of niacinamide and tetracycline was used to treat 31 dogs with various autoimmune skin diseases (discoid lupus erythematosus, pemphigus foliaceus, pemphigus erythematosus, and bullous pemphigoid). Of the 20 dogs with discoid lupus erythematosus, 70% had excellent or good response to treatment. Serious side effects were not noticed in any dog.     

Successful treatment of a novel generalized variant of canine discoid lupus erythematosus with oral hydroxychloroquine

Discoid lupus erythematosus (DLE) is a common canine autoimmune disease that usually manifests as a localized ulcerative and scarring nasal dermatitis. We report herein a generalized variant of canine DLE successfully treated with the antimalarial immunomodulator hydroxychloroquine (HCQ). A 9-year-old hairless Chinese crested dog was presented with annular and polycyclic hyperpigmented and scaly skin lesions with central erosions, hypopigmentation and/or scarring on the trunk, neck and lateral extremities. Associated systemic signs were not seen. The clinical diagnosis of generalized DLE was supported by the demonstration of lymphocyte-rich interface dermatitis with epidermal atrophy and dermo-epidermal deposition of immunoglobulins and activated complement. As for human DLE, treatment was initiated with HCQ at 5 mg/kg once daily along with 2 weeks of 0.1% tacrolimus ointment and restriction of sun exposure. Over the following year, complete remission was maintained with HCQ at 5 mg/kg orally once daily with the exception of three relapses; two occurred during treatment induction and the third arose when the frequency of HCQ administration was reduced to every other day. Disease flares were controlled with 0.1% tacrolimus ointment alternating with 0.1% prednicarbate cream once daily for 5-10 days. Altogether, adverse drug events were not seen with this regimen. In summary, clinically, histologically and immunologically, this dog's disease mirrored the generalized discoid variant of chronic cutaneous lupus erythematosus of humans. The apparent benefit of HCQ, its safety and low cost warrant future investigations of its use for treatment of canine cutaneous lupus variants.     

Squamous Cell Carcinoma Arising in Chronic Discoid Lupus Erythematosus Nasal Lesions in Two German Shepherd Dogs

Résumé— Un épithélioma spinocellulaire s'est développé sur des lésions chroniques incontrôlées de lupus erythémateux discoïde chez deux chiens bergers allemands. Les chiens n'avaient reçu ni traitement ni photoprotection pour leurs lésions de lupus discoïde durant les 4 à 6 ans précédant l'apparition clinique d'épithéliomas spinocellulaires. [Scott, D.W., Miller, W.H., Jr. Squamous cell carcinoma arising in chronic discoid lupus erythematosus nasal lesions in two German Shepherd Dogs (Un épithélioma spinocellulaire suivenant sur des lesions de lupus erythémateux discoïde chroniques chez deux bergers allemands).
Resumen— Dos perros de raza Pastor Alemán desarrollaron carcinomas de células escamosas en lesiones crónicas del tipo lupus eritematoso discoide. Estos animales no habian recibido tratamiento ni protección solar del cuadro de lupus eritematoso discoide en los 4 a 6 años previos al desarrollo del carcinoma escamoso. [Scott, D.W., Miller, W.H., Jr. Squamous cell carcinoma arising in chronic discoid lupus erythematosus nasal lesions in two German Shepherd Dogs (Carcinoma de células escamosas a partir de lesiones crónicas nasales del tipo lupus eritematoso discoide en dos perros Pastor Alemán).
Abstract— Squamous cell carcinoma developed in the chronic, uncontrolled nasal lesions of discoid lupus erythematosus in two German Shepherd Dogs. The dogs had received no treatment nor photoprotection for their discoid lupus erythematosus for 4–6 years prior to the clinical onset of squamous cell carcinoma.     

Discoid lupus erythematosus (DLE) in a Spitz dog

A 3-year-old, female Spitz, was presented due to lack of response to therapies with a 6-month history of skin lesions characterized by diffuse erythema and scaling on the dorsal trunk. Physical examination revealed the dog was active and healthy. Skin culture isolated no fungus. Histological examination of skin biopsy specimens revealed interface dermatitis with hydropic degeneration of the basal layers, predominant plasmacytic perivascular accumulation in the dermis, and intensive plasma cell-rich interface mural folliculitis. Moderate CD3-positive lymphocytes infiltrated the superficial dermis. This report may provide unique information of canine discoid lupus erythematosus in an unusual breed with atypical cutaneous lesions.     

Cosmetic rostral nasal reconstruction after nasal planum and premaxilla resection: technique and results in two dogs

Objective— To describe a novel reconstructive technique after nasal planum and premaxilla resection.
Study Design— Case report.
Animals— Dogs (n=2) with squamous cell carcinoma (SCC) of the nasal planum.
Methods— A 9-year-old neutered female Labrador retriever (dog 1) and an 11–year-old neutered male Golden retriever (dog 2) had resection of the nasal planum and premaxilla for treatment of locally invasive SCC. Reconstruction of a nasal planum facsimile was based on use of the nonhaired pigmented margins of bilateral labial mucocutaneous rotation-advancement flaps.
Results— Reconstruction of the premaxilla by construction of a nasal planum facsimile resulted in uncomplicated wound healing and improved cosmesis. There was no tumor recurrence at 1290 (dog 1) and 210 (dog 2) days after surgery.
Conclusion— Reconstruction of a nasal planum facsimile was successfully performed without complications in 2 dogs with high owner satisfaction with cosmetic appearance.
Clinical Relevance— This technique represents a significant advancement in surgical cosmetic outcome, may potentially reduce postoperative complications, and should be considered for dogs requiring nasal reconstruction after nasal planum resection with premaxillectomy.     

Comparison of three monoclonal and three polyclonal antibodies in the immunohistochemical diagnosis of canine autoimmune skin diseases

The aim of this study was to evaluate the utility of three monoclonal antibodies (mAbs), and two anticanine IgG and one anticanine IgM polyclonal antibodies (pAbs) for the immunohistochemical diagnosis of canine autoimmune skin diseases. Skin biopsies from 11 cases of pemphigus (7 foliaceus, 3 vulgaris and 1 erythematosus), 12 cases of discoid lupus erythematosus (DLE) and 12 cases of chronic hyperplasic dermatitis were used. The CA4E7 mAb (IgG1 + IgG2) showed similar sensitivity, but higher specificity and lower background than the two anti-IgG pAbs for the immunohistochemical diagnosis of pemphigus and DLE. The CA4F1 mAb (IgG2) and CA3H1 mAb (IgG2) showed moderate and low interepithelial reactivity, respectively, in autoimmune skin diseases, but strong staining of the cytoplasm of plasma cells of the inflammatory infiltrates. These results suggest that the CA4E7 mAb may be valuable in the immunohistochemical diagnosis of such disorders.     

Genotyping of Malassezia pachydermatis isolates from canine healthy skin and atopic dermatitis by internal spacer 1 (IGS1) region analysis

Isolates of Malassezia pachydermatis from healthy dog skin and from dogs with atopic dermatitis were molecularly characterized using internal spacer 1 (IGS1) region analyses, and their phospholipase A2 activity and pH growth profiles were then characterized in vitro. The percentage of isolates from healthy dogs that had the following IGS1 subtypes (isotype, %) were as follows: 1A, 6%; 1B, 27%; 1C, 11%; 2A, 6%; 2B, 6%; 3A, 11%; 3C, 3%; and 3D, 24%. In contrast, 9% of isolates from dogs with atopic dermatitis were isotype IB and 91% were isotype 3D, indicating that isolates of subtype 3D were the most prevalent in dogs with atopic dermatitis. Production of phospholipase A2 was statistically higher in isolates of subtype 3D than in the other subtypes. The subtype 3D isolates showed enhanced growth on alkaline medium compared with non-3D subtype isolates. The main clinical sign of canine Malassezia dermatitis is waxy exudates on the skin, which predispose the patient to development of a yeast overgrowth of the subtype 3D. Increased phospholipase A2 production may be involved in the inflammatory process associated with Malassezia dermatitis.     

Assessment of the ability of Malassezia pachydermatis to stimulate proliferation of canine keratinocytes in vitro

OBJECTIVE: To investigate the direct interaction between canine keratinocytes and live Malassezia pachydermatis and thereby determine the role of these organisms in the pathogenesis of epidermal hyperplasia associated with Malassezia dermatitis in dogs. SAMPLE POPULATION: Primary canine keratinocyte cultures established from skin samples obtained from clinically normal dogs. PROCEDURE: The proliferative response of keratinocytes co-cultured with Malassezia organisms for 1, 2, or 3 days was assessed by use of direct manual counting (to determine the number of keratinocytes in both the monolayer and the medium) and immunohistochemical staining techniques involving antibodies against proliferating cell nuclear antigen (PCNA) and another cellular proliferation marker, Ki-67. The potential cytotoxic effect of Malassezia organisms was investigated by use of an apoptosis detection kit to label keratinocytes co-cultured with M. pachydermatis that underwent apoptosis. RESULTS: No stimulatory effect of Malassezia organisms on canine keratinocyte proliferation was detected via cell counting and immunohistochemical techniques. However, there was a significant increase in dead keratinocytes in the medium with increasing numbers of Malassezia organisms in the co-culture. More apoptotic cells were observed in keratinocyte monolayers co-cultured with high numbers of M. pachydermatis than there were in monolayers cultured without Malassezia organisms, and the number increased after prolonged incubation. CONCLUSIONS AND CLINICAL RELEVANCE: M. pachydermatis did not stimulate canine keratinocyte proliferation in vitro. The results suggested that the epidermal hyperplasia observed in dogs with Malassezia dermatitis is unlikely to be caused by a direct effect of the organism on the keratinocyte cell cycle, but is likely to involve other mechanisms.