27.09.2017 

Putative contact ketoconazole shampoo-triggered pemphigus foliaceus in a dog.

Sung HJ, Yoon IH, Kim JH. Can Vet J. 2017 Sep;58(9):914-918.

A 10-year-old spayed female cocker spaniel dog was referred for an evaluation of acute-onset generalized pustular cutaneous lesions following application of ketoconazole shampoo. Cytologic and histopathologic examinations of the lesions revealed intra-epidermal pustules with predominantly neutrophils and acantholytic cells. This is the first description of putative contact ketoconazole shampoo-triggered pemphigus foliaceus in a dog.

Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study.

Sundburg CR, Belanger JM, Bannasch DL, Famula TR, Oberbauer AM. BMC Vet Res. 2016 Dec 8;12(1):278.

Gonadectomy is one of the most common procedures performed on dogs in the United States. Neutering has been shown to reduce the risk for some diseases although recent reports suggest increased prevalence for structural disorders and some neoplasias. The relation between neuter status and autoimmune diseases has not been explored. This study evaluated the prevalence and risk of atopic dermatitis (ATOP), autoimmune hemolytic anemia (AIHA), canine myasthenia gravis (CMG), colitis (COL), hypoadrenocorticism (ADD), hypothyroidism (HYPO), immune-mediated polyarthritis (IMPA), immune-mediated thrombocytopenia (ITP), inflammatory bowel disease (IBD), lupus erythematosus (LUP), and pemphigus complex (PEMC), for intact females, intact males, neutered females, and neutered males. Pyometra (PYO) was evaluated as a control condition.

Patient records (90,090) from the William R. Pritchard Veterinary Medical Teaching Hospital at the University of California, Davis from 1995 to 2010 were analyzed in order to determine the risk of immune-mediated disease relative to neuter status in dogs. Neutered dogs had a significantly greater risk of ATOP, AIHA, ADD, HYPO, ITP, and IBD than intact dogs with neutered females being at greater risk than neutered males for all but AIHA and ADD. Neutered females, but not males, had a significantly greater risk of LUP than intact females. Pyometra was a greater risk for intact females. The data underscore the importance of sex steroids on immune function emphasizing a role of these hormones on tissue self-recognition. Neutering is critically important for population control, reduction of reproductive disorders, and offers convenience for owners. Despite these advantages, the analyses of the present study suggest that neutering is associated with increased risk for certain autoimmune disorders and underscore the need for owners to consult with their veterinary practitioner prior to neutering to evaluate possible benefits and risks associated with such a procedure.

This article is available as a free download under  www.ncbi.nlm.nih.gov. When you evaluate this data, you will see that the odds to develop some of those diseases doubles, which sounds dramatic, but when you look at the prevalence data, it means, that instead of 1 in 100,000 dogs getting the disease it doubles to 1 in 50,000 dogs...

Oral glucocorticoid pulse therapy for induction of treatment of canine pemphigus foliaceus - a comparative study.

Bizikova P, Olivry T. Vet Dermatol. 2015 Oct;26(5):354-8, e76-7. doi: 10.1111/vde.12241.

The management of canine pemphigus foliaceus (PF) often requires long-term immunosuppressive treatment that is often associated with unacceptable adverse effects. High-dose glucocorticoid pulse therapy, an alternative protocole used for pemphigus in people, has been shown to provide rapid improvement in dogs with pemphigus foliaceus and vulgaris. To further identify the benefit of pulse therapy for management of canine PF, we compared the outcomes of oral glucocorticoid pulse and traditional therapies during the first 3 months of disease management. Dogs were allocated based on their oral glucocorticoid regimen during the first 12 weeks of PF management into the 'traditional' (20 dogs) or the 'pulse' (18 dogs) treatment groups.

The proportion of dogs achieving complete remission (CR) during the first 12 weeks of treatment was significantly higher for the 'pulse' (61%) than for the 'traditional' group (15%; P = 0.0063). The maximal oral glucocorticoid dosage given to dogs from the 'traditional' group was significantly higher (median: 3.2 mg/kg) than that given between pulses to dogs from the other group (median: 1.1 mg/kg; P < 0.0001). There was no significant difference between groups in the time needed to achieve CR, the proportion of dogs requiring adjuvant immunosuppressive treatment or in the proportion of dogs experiencing severe adverse drug reactions. These results suggest several benefits associated with oral glucocorticoid pulse therapy, such as a higher proportion of dogs achieving CR during the first 3 months, a lower average maximal oral glucocorticoid dosage given between pulses and minimal adverse drug events.

Dinotefuran/pyriproxyfen/permethrin pemphigus-like drug reaction in three dogs.

Bizikova P, Moriello KA, Linder KE, Sauber L. Vet Dermatol. 2015 Jun;26(3):206-8, e45-6. doi: 10.1111/vde.12202.

Pemphigus foliaceus (PF) can occur spontaneously or as a reaction pattern associated with cutaneous adverse drug reactions. This report provides clinical, histological and immunological assessments of three dogs that developed cutaneous adverse drug reactions following application of a topical flea and tick control product, which contained dinotefuran, pyriproxyfen and permethrin. The dogs exhibited rapid onset of papules, pustules and crusts at the site of application of the flea control product. In two dogs, the lesions became generalized, while the third exhibited a localized phenotype. Both dogs with generalized lesions required immunosuppressive treatment; one achieved remission after 1 year of treatment and one was euthanized due to adverse effects of glucocorticoids. The dog with a localized phenotype was treated with topical glucocorticoids exclusively and achieved remission after 10 months. Histology revealed subcorneal pustular dermatitis, with acantholysis of keratinocytes and focal to multifocal full-thickness epidermal necrosis. These features are similar to those previously reported for pesticide-triggered and spontaneous PF. Tissue-bound IgG was detected in two of three dogs, and autoantibodies targeting canine desmocollin-1 were identified in the serum of the one dog from which a sample was available. Cutaneous adverse drug reaction caused by a flea control product containing dinotefuran, pyriproxyfen and permethrin closely resembled those reported for other pesticide-associated PF-like cutaneous adverse drug reactions. Although it appears to be a rare entity, clinicians and pathologists should be aware of the potential for flea and tick control products to trigger PF-like reactions.

Therapeutic effectiveness of calcineurin inhibitors in canine vesicular cutaneous lupus erythematosus.

Banovic F, Robson D, Linek M, Olivry T. Vet Dermatol. 2017 Oct;28(5):493-e115. doi: 10.1111/vde.12448.

Oral and topical calcineurin inhibitors (CIs) have been reported to lead to complete lesion remission in several dogs with vesicular cutaneous lupus erythematosus (VCLE). This study reports retrospectively on the effectiveness and adverse effects of systemic (ciclosporin) and/or topical (tacrolimus/pimecrolimus) CIs in 11 dogs with VCLE. Inclusion criteria were: (i) presence of characteristic annular, polycyclic or serpiginous ulcerations distributed over the groin, axillae and/or ventral abdomen; (ii) a histopathological diagnosis of VCLE (i.e. a lymphocyte-rich interface dermatitis with vesiculation); (iii) treatment that included CIs for at least eight weeks; and (iv) follow-up until death/euthanasia or for a minimum of 12 months post-diagnosis. Initial therapy included the avoidance of excessive sun exposure, oral glucocorticoids [six of 11 dogs (55%); progressively tapered over a month] and once daily ciclosporin [11 dogs (100%); median 5.8 mg/kg]. A complete remission (CR) of signs occurred between days 35 and 70 after starting CIs in eight dogs (73%); increasing ciclosporin dosage and adding topical tacrolimus induced a CR in two additional dogs (18%). Relapses were common when doses were tapered or discontinued. With the exception of three dogs that were euthanized, clinical signs were maintained in CR with oral ciclosporin (eight of eight dogs treated, 100%) or topical tacrolimus/pimecrolimus (four of eight dogs; 50%) with a median follow-up of 2.9 years. These observations support CIs as the preferable therapeutic alternatives to long-term immunosuppression with oral glucocorticoids in dogs with VCLE.

A retrospective study comparing histopathological and immunopathological features of nasal planum dermatitis in 20 dogs with discoid lupus erythematosus or leishmaniosis.

De Lucia M, Mezzalira G, Bardagí M, Fondevila DM, Fabbri E, Fondati A. Vet Dermatol. 2017 Apr;28(2):200-e46. doi: 10.1111/vde.12419.

In areas endemic for leishmaniosis, discoid lupus erythematosus (DLE) and canine leishmaniosis (CanL) are the most common differential diagnoses for nasal planum erosive-ulcerative dermatitis in dogs. This study compares histopathological and immunopathological features of canine nasal planum erosive-ulcerative dermatitis with depigmentation due to DLE or CanL. Nasal planum biopsies from dogs with nasal planum loss of architecture, depigmentation, swelling, erosions or ulcerations due to DLE (n = 14) or CanL (n = 6) were included. Sections of paraffin-embedded samples, stained with haematoxylin and eosin were reviewed. Samples were examined using antibodies targeting T cells (CD3), B cells (CD20), macrophages (Mac387) and class II major histocompatibility complex (MHC II). Histopathological and immunophenotypical findings were compared between DLE and CanL cases. Lichenoid and interface dermatitis were observed in both DLE and CanL cases. A nodular-to-diffuse, superficial and/or deep dermatitis with macrophages, lymphocytes and plasma cells was present only in CanL samples. CD20-positive cells predominated over CD3- and Mac387-positive cells in the two conditions. The percentage of dermal Mac387-positive cells was higher in CanL compared to DLE samples and the difference was statistically significant (P = 0.025). In this study, similar histopathological and immunopathological findings were observed in dogs with nasal planum lesions due to DLE or CanL. Therefore, in areas endemic for leishmaniosis, the presence of the parasite should be investigated in canine nasal planum dermatitis showing clinical and histopathological features suggestive of DLE.

Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases).

Banovic F, Linder KE, Uri M, Rossi MA, Olivry T. Vet Dermatol. 2016 Dec;27(6):488-e131. doi: 10.1111/vde.12389.

Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized. We report herein the signalment, clinical signs, treatment outcome, histopathology and immunological findings of 10 dogs with GDLE. Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recurrent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich interface dermatitis). Direct immunofluorescence (IF) and antinuclear antibody serology were investigated whenever possible. Various breeds were affected in their mid- to late adulthood. Selection criteria of generalized multifocal, annular ("discoid") to polycyclic plaques with pigment changes, erythematous margin, adherent scaling, follicular plugging and central alopecia were shown in all dogs. In nine dogs, plaques contained mild to moderate central scarring with depigmentation and/or hyperpigmentation. There were no dogs in which the disease progressed to systemic lupus erythematosus within a median follow-up of 2.5 years. Per inclusion criteria, interface dermatitis occurred with basement membrane zone (BMZ) thickening, suprabasal apoptosis and/or dermal fibrosis in some dogs. Infundibular interface folliculitis was common; it sometimes transitioned to mural folliculitis in lower follicle segments, and occurred with follicular and sebaceous gland atrophy. The direct IF revealed patchy deposition of immunoglobulin IgG and IgM at the BMZ. Lesions responded to a variety of treatments, including ciclosporin, hydroxychloroquine, topical tacrolimus and tetracycline/ niacinamide. Relapses were common after medications were tapered. These observations support the existence of a canine homologue of human GDLE.

Peculiarities of feline hyperadrenocorticism: Update on diagnosis and treatment.

Boland LA, Barrs VR. J Feline Med Surg. 2017 Sep;19(9):933-947. doi: 10.1177/1098612X17723245.

Practical relevance: Hyperadrenocorticism (HAC) is a relatively uncommon endocrinopathy of older cats, with a mean age at diagnosis of 10 years. In addition to pituitary-dependent and adrenal-dependent hypercortisolism, clinical signs of HAC can result from adrenal sex steroid-producing tumours. Clinical challenges: While HAC in cats has many similarities to canine HAC, there are key differences in presentation, diagnosis and response to therapy.

Most, but not all, cats with HAC have concurrent diabetes mellitus, which is often insulin resistant. Up to a third of cats with HAC have extreme skin fragility and are at high risk of debilitating iatrogenic skin tears during diagnostic or therapeutic interventions. Infections of the skin and nail beds, and urinary, respiratory and gastrointestinal tract, secondary to cortisol-induced immune suppression, are also common. Cats respond differently to dogs to adrenal function tests including adrenocorticotropic hormone (ACTH) stimulation and dexamethasone suppression tests; a 10-fold higher dose of dexamethasone is recommended in cats to screen for HAC. Curative treatment options include adrenalectomy or transsphenoidal hypophysectomy. Radiation or medical treatment may improve clinical signs. The response to mitotane therapy is poor. While trilostane is the medical treatment of choice based on retrospective studies, investigations into the pharmacokinetics of this drug in cats are lacking.

Global importance: Feline HAC occurs worldwide and is not associated with any purebreed predisposition. Although uncommon, adrenal sex steroid-producing tumours have a higher prevalence in cats than in dogs. Evidence base: The information in this review is drawn from over 180 reported cases of feline HAC. Reports investigating clinical presentation, clinicopathological findings and treatment outcomes are observational, retrospective multiple case series (EBM grade III) or single case reports (EBM grade IV). While most endocrine testing studies for diagnosis are cohort controlled analytical studies (EBM grade III), prospective, randomised, placebo-controlled studies have been performed (EBM grade I).

Comparison of Survival Times for Dogs with Pituitary-Dependent Hyperadrenocorticism in a Primary-Care Hospital: Treated with Trilostane versus Untreated.

Nagata N, Kojima K, Yuki M. J Vet Intern Med. 2017 Jan;31(1):22-28. doi: 10.1111/jvim.14617.

BACKGROUND: Although pituitary-dependent hyperadrenocorticism (PDH) is one of the most common endocrinopathies in dogs, the effects of withholding treatment on survival time in dogs with PDH remain unclear.

HYPOTHESIS/OBJECTIVES: The purpose of this study was to clarify the effects of treatment in dogs with PDH by comparing survival times between dogs treated with trilostane and untreated dogs.

ANIMALS: Forty-three dogs diagnosed with PDH at a primary-care hospital in Japan between June 2009 and January 2014.

METHODS: Retrospective cohort study. The medical records of dogs with PDH treated with trilostane (n = 17) or left untreated (n = 26) were reviewed retrospectively. Survival analysis at 2 years after diagnosis of PDH was performed.

RESULTS: Median survival time for the trilostane group was not reached (95% confidence interval [CI], 443 days-not applicable) and was significantly longer than the 506 days (95% CI, 292-564 days; P = .016) for the untreated group. Multivariate Cox proportional hazards analysis (including age at diagnosis, basal cortisol concentration at diagnosis, and treatment group) only identified assignment to the untreated group (hazard ratio, 5.01; 95% CI, 1.63-15.44) as associated with increased mortality.

CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this retrospective cohort study suggest that withholding treatment for dogs with PDH might be associated with a higher risk of death. This represents the largest study to date to report survival times of untreated dogs with PDH.

This article can be downloaded without extra charge under:  www.ncbi.nlm.nih.gov

Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs.

Macfarlane L, Parkin T, Ramsey I. Vet Rec. 2016 Dec 10;179(23):597. doi: 10.1136/vr.103744.

It is recommended that trilostane therapy of canine hyperadrenocorticism is monitored using an ACTH stimulation test, however this has never been validated. Three cortisol concentrations (pre-trilostane, 3-hour posttrilostane and 1-hour post-ACTH stimulation) were compared to a clinical score obtained from an owner questionnaire. There were 110 sets of 3 cortisol measurements and questionnaires obtained from 67 trilostane treated dogs. Questionnaire results were used to classify each dog as well or unwell. Well dogs were then categorised as having excellent, moderate or poor hyperadrenocorticism control, using thresholds produced by 14 independent veterinarians. Correlation co-efficients were used to compare the three cortisol concentrations to the owner score and the Kruskal Wallis and Mann-Whitney U tests were used to compare the three cortisol concentrations between categories of control. Cortisol cut-off values between significantly different categories were determined using ROC curves. Pre-trilostane and 3-hour post-trilostane cortisol were better correlated to the owner score and had cut-offs to differentiate between categories of control that had superior sensitivity and specificity results, than the post-ACTH cortisol. Iatrogenic hypoadrenocorticism was not detected in any unwell dog. This study shows that the pre-trilostane and 3-hour post-trilostane cortisol are potentially better monitoring methods than the ACTH stimulation test.

This article can be downloaded without extra charge under:  www.ncbi.nlm.nih.gov

Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment.

Boretti FS, Holzthüm J, Reusch CE, Sieber-Ruckstuhl NS. Schweiz Arch Tierheilkd. 2016 Sep;158(9):631-638. doi: 10.17236/sat00083.

Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

This article comes to different conclusions than the above-mentioned article because it already assumes that the ACTH stimulation test is the gold standard. It can be downloaded without extra charge under:  sat.gstsvs.ch (PDF)

Effects of Levothyroxine Administration and Withdrawal on the Hypothalamic-Pituitary-Thyroid Axis in Euthyroid Dogs.

Ziglioli V, Panciera DL, Troy GC, Monroe WE, Boes KM, Refsal KR.

J Vet Intern Med. 2017 May;31(3):705-710. doi: 10.1111/jvim.14711. Epub 2017 Apr 22.

Chronic supplementation can suppress the hypothalamic-pituitary-thyroid axis (HPTA) and make it difficult to assess thyroid function after withdrawal of levothyroxine. The objective of this study was to determine whether the HPTA is suppressed after levothyroxine administration in euthyroid dogs and the time required for resolution of any suppression. A prospective, randomized study administering levothyroxine to 28 euthyroid dogs for 8 weeks (group 1) or 16 weeks (group 2). Serum concentrations of total thyroxine (T4 ), free thyroxine (fT4 ) by equilibrium dialysis, thyroid stimulating hormone; thyrotropin (TSH), and 3,5,3'-triiodothyronine (T3 ) were measured every 4 weeks during supplementation and for 16 weeks after levothyroxine was discontinued. Mean serum concentrations of T4 and fT4 were significantly higher (P < .0001) and TSH was lower (P < .0001) in all dogs during levothyroxine administration compared to baseline. Mean serum concentrations of T4 , fT4, and TSH in both groups, beginning 1 week after levothyroxine was discontinued, were significantly different (P < .01) compared to values during levothyroxine administration but not compared to baseline values (P > .3). Assessing thyroid function tests 1 week after cessation of levothyroxine at 26 μg/kg once a day for up to 16 weeks will provide an accurate assessment of thyroid function in healthy euthyroid dogs.

This article shows, that the thyroid gland does not completely shut down within 8 weeks of supplementaiton with T4 and can be downloaded without extra charge under:  www.ncbi.nlm.nih.gov

 -Vorstand