Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca

Objective To investigate the effect of 0.02% tacrolimus in aqueous suspension on tear production in dogs with keratoconjunctivitis sicca (KCS). Animals studied One hundred five dogs diagnosed with KCS [Schirmer tear test (STT) ≤ 10 mm/min and clinical signs of dry eye]. Eyes with marginally decreased STT (11 ≤ 15 mm/min) and clinical signs of dry eye were also evaluated. Procedure The investigation was conducted in two parts: an initial efficacy study and a subsequent double blinded controlled study. In the efficacy study, the effect of topical tacrolimus (formerly FK‐506) on tear production in dogs with primary KCS was evaluated. Dogs were divided into four categories: 1) 59 eyes (38 dogs) naïve to tear stimulation therapy with initial STT ≤ 10 mm/min; 2) 28 eyes (21 dogs) naïve to tear stimulation therapy with initial STT 11 ≤ 15 mm/min; 3) 30 eyes (15 dogs) maintained successfully on CsA therapy; 4) 47 eyes (24 dogs) unresponsive to CsA therapy. STT and clinical signs were evaluated prior to and after 6 to 8 weeks of twice daily tacrolimus administration. Tacrolimus was substituted for CsA therapy in categories 3 and 4. The controlled study compared the effect of topical tacrolimus in aqueous suspension to administration of the aqueous carrier alone on tear production in 20 dogs with primary KCS. Results In the efficacy study, STT increased by 5 mm/min in 84.7%, 25.0%, 26.7% and 51.1% of eyes in categories 1, 2, 3 and 4 respectively after tacrolimus administration. Eighty‐three percent of eyes with extremely low initial STT (≤ 2 mm/min), increased 5 mm/min after tacrolimus. In the controlled study, STT increased by 5 mm/min in 7/10 dogs (14/20 eyes) that received tacrolimus and in none of the 10 dogs that received aqueous carrier alone. Dogs receiving just the aqueous carrier were subsequently treated with tacrolimus, and STT increased 5 mm/min in 9 dogs (18/20 eyes) after administration. Conclusions Twice daily administration of 0.02% tacrolimus in aqueous suspension effectively increased tear production in dogs with KCS. Topical tacrolimus is a promising alternative to topical CsA for treatment of KCS and may be beneficial in patients with less than optimal response to topical CsA.     

Clinical evaluation of pimecrolimus eye drops for treatment of canine keratoconjunctivitis sicca: a comparison with cyclosporine A

The aim of this study was to evaluate the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs and to compare the efficacy with that of cyclosporine A (CsA) ointment. An open-label, multicenter study enrolling 44 dogs previously untreated with CsA was conducted. Dogs were randomly assigned to a treatment group and medicated twice daily for 8 weeks. After that time the mean increase (+/-SEM) in the Schirmer tear test was 9.2+/-1.6 mm/min in the pimecrolimus group and 5.8+/-1.1 mm/min in the CsA group (P=0.085). The improvement in clinical signs of inflammation in eyes treated with pimecrolimus was significantly greater than in eyes treated with CsA (P=0.02). The results show that 1% pimecrolimus oily eye drops are as safe as and more effective than CsA ointment in controlling KCS in dogs.     

Histologic characteristics and local cellular immunity of the gland of the third eyelid after topical ophthalmic administration of 2% cyclosporine for treatment of dogs with keratoconjunctivitis sicca

OBJECTIVE: To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. ANIMALS: 24 dogs with bilateral KCS. PROCEDURE: Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. RESULTS: Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE: Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.     

Characterization of lacrimal gland lesions and possible pathogenic mechanisms of keratoconjunctivitis sicca in dogs with leishmaniosis

In a previous study, it was found that 2.8% of dogs with leishmaniosis had keratoconjunctivitis sicca (KCS). The aim of this study was to characterize the lesions present in the lacrimal glands of dogs with leishmaniosis and to determine the presence of the parasite by means of immunohistochemistry. The inflammatory infiltrate was described as granulomatous or pyogranulomatous and was located around the ductal component of the glands. Immunoperoxidase staining localized the parasites following the same pattern. Samples from eyes that had clinical signs compatible with KCS presented inflammatory infiltrate and parasite more commonly than those from eyes without clinical signs. One of the mechanisms of KCS in dogs with leishmaniosis may be the inflammatory infiltrate located around the ducts of lacrimal glands, producing retrograde accumulation and retention of secretion. Meibomian gland was the most commonly affected by the infiltrate, highlighting the possibility of a qualitative KCS in these dogs.     

Keratoconjunctivitis sicca associated with administration of etodolac in dogs: 211 cases (1992-2002)

OBJECTIVE: To characterize features and response to treatment of keratoconjunctivitis sicca (KCS) associated with oral administration of etodolac in dogs. DESIGN: Retrospective case series. SAMPLE POPULATION: 65 cases obtained from a survey of veterinary ophthalmologists (group A) and 146 cases reported to Fort Dodge Animal Health (group B). PROCEDURES: Data analyzed included breed, sex, age, weight, dose and duration of etodolac administration, results of Schirmer tear test at the time of diagnosis and last follow-up, treatments, and response to treatments. Groups A and B were analyzed separately by use of forward stepwise logistic regression models developed to predict probability of complete remission or clinical improvement as a function of several variables. RESULTS: Most dogs developed severe KCS (84 eyes of 50 dogs [group A]; 111 eyes of 62 dogs [group B]). Resolution of KCS occurred in 7 of 65 (A) and 23 of 146 (B) dogs. No response to treatment was observed in 26 of 65 (A) and 27 of 146 (B) dogs. Fifty-one (A) and 52 (B) dogs had records that were sufficiently complete to use in models. In group B, dogs with etodolac treatment intervals < 6 months prior to the onset of KCS were 4.2 times as likely to have remission as were dogs with treatment intervals > or = 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: Shorter duration of etodolac administration (< 6 months) was associated with improved outcome in 1 population of dogs. Monitoring of tear production should be considered prior to and during administration of etodolac in dogs.     

A systematic review and meta-analysis of the efficacy and safety of cyclosporin for the treatment of atopic dermatitis in dogs

The efficacy of cyclosporin A (CsA) for the treatment of canine atopic dermatitis was evaluated based on the systematic review of prospective clinical trials published between 2001 and 2005. Ten studies with adequate design characteristics were included. These studies enrolled 799 dogs, 672 (84%) treated with CsA, 160 (20%) with placebo, 74 (9%) with oral glucocorticoids and 23 (3%) with antihistamines. Treatment duration varied from 2 weeks to 6 months. For safety analysis, data were available from 660 dogs. Lesion scores were improved from baseline in the range of 30-52%, 53-84% and 52-69% after 4, 6 and 16 weeks, respectively. The percentage of dogs with only mild pruritus rose from 0-13% at inclusion to 32-59% and 46-90% after 4 and 12 weeks, respectively. In most studies, the frequency of CsA administration could be reduced to every other day in 40% to 50% of patients after 4 weeks and to twice weekly in 20-26% of the dogs after 12-16 weeks. Meta-analysis confirmed highly significant effects of CsA compared to placebo, but none between oral CsA and glucocorticoids. The initial disease severity, age or body weight of subjects did not influence treatment success. Improvement by more than 50% over baseline of lesion scores was predictive of a better response during treatment maintenance. Vomiting and soft stools/diarrhoea were the most frequent adverse events seen at least once during the studies. These occurred in 25% and 15% of subjects, respectively. The frequency of each other type of adverse events was lower than 2.1%. In summary, the administration of CsA for the treatment of canine AD was found to be as effective as that of glucocorticoids, and adverse effects were minimal.     

Canine neurogenic Keratoconjunctivitis sicca: 11 cases (2006-2010)

Objective To describe the clinical data of dogs with neurogenic Keratoconjunctivitis sicca (KCS) and an ipsilateral dry nose without other neurologic deficits. Procedure The retrospective case study included 11 dogs diagnosed with neurogenic KCS and an ipsilateral dry nose between 2006 and 2010. Medical records were reviewed for breed, age, sex, history, suspected cause of neurogenic KCS, clinical signs, and treatment modalities. Follow‐up information was obtained by re‐examination of patients or completion of a telephone survey with the referring veterinarian or the owners. Results Mean age of the dogs was 6.6 ± 4.5 years. Neurogenic KCS was diagnosed in three females, five spayed females, one male, and two castrated males representing 10 different breeds. Ophthalmic signs of KCS (mean Schirmer tear test [STT] value of 1.9 ± 2.9 mm/min) combined with an ipsilateral dry nose were diagnosed in seven left and four right eyes. The suspected cause of neurogenic KCS was idiopathic in nine and trauma in two cases. Systemic therapy consisted of oral pilocarpine 1–2% eye drops combined with case‐specific topical treatment with cyclosporine 0.2% and tear substitutes. Duration of systemic treatment with pilocarpine until healing was 125 days (range 84–204, median 98 days) for five dogs. One dog was lost to follow‐up, and the remaining five dogs are still under systemic treatment with pilocarpine. Conclusions Neurogenic KCS with an ipsilateral dry nose seems to be a predominantly idiopathic disease of middle‐aged female dogs without breed predisposition, which may be self‐limiting in some cases.     

Long-term use of cyclosporine in the treatment of canine atopic dermatitis

This retrospective study of 51 dogs with atopic dermatitis (AD) treated with cyclosporine (CsA) for a minimum of 6 months assessed the frequency of dosing and the need for continual treatment to control clinical signs. The study evaluated both medical records and information supplied by the owners in the form of written questionnaires and telephone follow-up. Laboratory parameters, possible adverse effects and owner satisfaction were assessed. The dose of CsA was 5 mg/kg orally per day and dogs received CsA for 6-30 months. At the conclusion of the study period, 28 dogs (55%) needed ongoing CsA to control clinical signs of AD: 8 (15%) received CsA 2-3 days per week, 10 (20%) 4-5 days per week, and 10 (20%) daily. CsA was discontinued in 23 dogs (45%) after 6-24 months due to either a limited response (22%) or after achieving a clinical response (24%). The results suggest that some dogs with AD treated with CsA may not require daily or even ongoing treatment to control clinical signs. Laboratory abnormalities were detected in 13 dogs (25%) during their CsA treatment. Two dogs developed oral growths and three developed hirsuitism. Forty owners (78%) reported no adverse events in their dogs during the treatment period. Thirty-six owners (71%) were satisfied with CsA as treatment for their atopic dog.     

A topical aqueous calcineurin inhibitor for the treatment of naturally occurring keratoconjunctivitis sicca in dogs

Purpose The purpose of this study was to evaluate the efficacy of an aqueous calcineurin inhibitor, SCY‐641, in the treatment of naturally occurring canine immune‐mediated keratoconjunctivitis sicca (KCS). Methods A randomized, double‐masked, placebo‐controlled clinical study of 56‐day duration was performed in dogs with naturally occurring immune‐mediated KCS assigned to treatment with either topical twice‐daily aqueous calcineurin inhibitor solution (SCY‐641) or artificial tears (placebo) by the study administrator. Clinical examination and Schirmer tear tests (STT) were performed prior to therapy and at days 7, 14, 28, and 56 after initiation of treatment. Results Twenty dogs were enrolled in the study with ten receiving placebo and 10 receiving SCY‐641 in one or both eyes. No adverse effects were noted with any treatment. There were no significant differences in mean STT values in dogs in group either at day 0 (prior to therapy) or after 7 days of treatment. At 14, 28, and 56 days after initiation of treatment, mean STT and increase in STT over baseline in dogs treated with SCY‐641 were significantly higher than in dogs treated with placebo (P < 0.04). Conclusions SCY‐641 was well tolerated by dogs with naturally occurring KCS, and by 14 days after initiating therapy, dogs treated with SCY‐641 had significantly higher STT than placebo‐treated dogs. These preliminary results indicate that topical SCY‐641, in a stable clear aqueous solution, is efficacious in a spontaneous model of KCS and warrants further evaluation as a treatment of immune‐mediated KCS.     

Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease

AIM: To evaluate the efficacy and tolerance of an extract of green-lipped mussel (GLME) in the management of mild-to-moderate degenerative joint disease (DJD) in dogs. METHODS: Eighty-one dogs presumptively diagnosed with DJD were treated orally daily with either GLME or a placebo for 56 days, in a double-blind, placebo-controlled study. In an uncontrolled open-label extension to the study, all dogs were treated with GLME for an additional 56 days (from Days 57-112). Clinical signs were subjectively scored by the owners, and findings of detailed musculoskeletal examinations were scored by one veterinarian. Efficacy was assessed from a qualitative comparison of the proportion of dogs with improved clinical signs, and a quantitative comparison of the scores of the musculoskeletal examinations, between groups. Haematological and biochemical analyses and reports by owners of possible adverse drug reactions were used to screen for evidence of toxicity. RESULTS: There was close agreement between assessments by the veterinarian and owners. The clinical signs of DJD in both GLME-treated and placebo groups improved significantly over baseline by Day 28; this improvement continued over the entire course of the study. There were no significant differences between groups on Day 28. On Day 56, a higher proportion of dogs in the GLME-treated group had improved clinical signs (p=0.018), and GLME-treated dogs had marginally better (p=0.053) musculoskeletal scores than dogs in the placebo group. The differences between the groups were no longer apparent by Day 112, by which time the former placebo group had been receiving GLME for 56 days in the open-label phase of the study. The proportion of dogs in the former placebo group that had improved by Day 112 (29/32; 91%) was significantly greater (p=0.012) than the proportion improved at Day 56 (15/37; 41%). No signs of toxicity were apparent. CONCLUSIONS AND CLINICAL RELEVANCE: GLME had a beneficial effect on the clinical signs of dogs presumptively diagnosed with mild-to-moderate DJD. Long-term therapy may be required before improvement is apparent.     

Clinical findings in 40 dogs with hypersensitivity associated with administration of potentiated sulfonamides

The purpose of this study was to summarize the clinical findings in 40 dogs with systemic hypersensitivity reactions associated with the administration of potentiated sulfonamides. Dogs ranged from 6 months to 14 years of age, with a mean of 5.7 +/- 3.2 years. Spayed female dogs were overrepresented (24 of 40, or 60% of the dogs), as were Samoyeds (3 of 40; 8%) and Miniature Schnauzers (5 of 40; 13%). Mean dosages of potentiated sulfonamides were 47.0 +/- 14.9 mg/kg/d (range, 23.4-81.4 mg/kg/d). The time from the 1st administration of the drug to the onset of the clinical signs of hypersensitivity ranged from 5 to 36 days, with a mean of 12.1 +/- 5.9 days. There was no relationship between either the dosage or type of sulfonamide given and the time to the onset of the clinical signs. Fever was the most common clinical sign observed (55% of the dogs); thrombocytopenia was 2nd (54%), and hepatopathy (28%) was 3rd. Neutropenia, keratoconjunctivitis sicca (KCS), hemolytic anemia. arthropathy, uveitis, skin and mucocutaneous lesions, proteinuria, facial palsy, suspected meningitis, hypothyroidism, pancreatitis, facial edema, and pneumonitis were also observed in some patients. Of 39 dogs with adequate follow-up, 30 (77%) recovered, whereas 8 (21%) either died or were euthanized, and 1 recovered clinically but had persistent increases in alanine aminotransferase (ALT) activity. Dogs with hepatopathy generally had a poorer prognosis (46% recovery) than dogs without hepatopathy (89% recovery; P = .0035). Sixty-three percent of the dogs with thrombocytopenia recovered, compared to 90% of the dogs without thrombocytopenia (P = .042). Recovery was not associated with sex, age, breed, or type of sulfonamide administered.     

Evaluation of the presence of Leishmania spp. by real-time PCR in the lacrimal glands of dogs with leishmaniosis

Leishmania infantum infection is highly prevalent in endemic areas. Dogs with leishmaniosis may develop keratoconjunctivitis sicca (KCS). The goals of this study were (1) to quantify Leishmania amastigotes in the Meibomian glands (MG), main lacrimal gland (MLG) and nictitating membrane gland (NMG) from dogs with leishmaniosis; (2) to compare these results to immunohistochemistry (IHC), and (3) to explore the association between the Leishmania parasite load and the presence of ocular clinical signs. Twenty-five dogs diagnosed with leishmaniosis were included. MG, MLG and NMG from both eyes were collected. Histopathology, IHC and real-time PCR were performed. All specimens yielded positive real-time PCR results. For all three glands, samples from dogs with ocular clinical signs had mean ΔCt (cycle threshold) values significantly lower (higher parasite loads) than those from dogs without signs. Cut-off values of ΔCt<0, ΔCt<4 and ΔCt<4.9 for MG, MLG and NMG, resulted in a likelihood ratio of positives of 5.9, 6.38 and 6.38, respectively. Samples with ΔCt values below the reported cut-off were significantly more likely to display clinical signs related to KCS than those with results above the cut-off, for all three glands. Similarly, ΔCt values below the cut-off were significantly associated with positive IHC. In this study real-time PCR has been standardised for use in MG, MLG and NMG. A cut-off value established for each of these tissues may aid the clinician in the discrimination between ocular signs related to Leishmania from those associated with other causes of KCS.     

Cyclosporine decreases skin lesions and pruritus in dogs with atopic dermatitis: a blinded randomized prednisolone-controlled trial

During the last decade, oral cyclosporin (CsA) has proven to be effective, in randomized controlled trials, for the treatment of atopic dermatitis (AD) in human patients. The purpose of this blinded randomized controlled trial was to test the hypothesis that CsA was successful in reducing the gravity of clinical signs of AD in dogs. Thirty dogs with nonseasonal AD were randomly allocated to receive an oral solution of either NEORAL CsA (5 mg kg-1) or prednisolone (0.5 mg kg-1) once daily for 6 weeks. Before, and 3 and 6 weeks after therapy, skin lesions were graded by clinicians using the Canine AD Extent and Severity Index (CADESI). Pruritus was assessed by the owners using a visual analog scale (PVAS). In both groups, CADESI and PVAS values were significantly lower at 6 weeks post treatment than before the initiation of therapy (Friedman test, P < 0.0004). The percentage reductions in CADESI and PVAS values from baseline were not statistically different between groups (Mann-Whitney test, P > 0.3). In this experiment, the tolerability and safety of oral CsA and prednisolone appeared similar. One-fifth of dogs given oral CsA occasionally developed diarrhoea or soft stools. One dog that was given CsA developed a generalized papillomatous skin eruption during the second half of the trial. Our study provides randomized controlled trial evidence that CsA reduces the severity of clinical signs in dogs with nonseasonal AD. Moreover, the anti-allergic efficacy of CsA appears comparable with that of prednisolone. We propose that oral CsA should be considered as a valuable alternative to glucocorticoid therapy in dogs with AD.     

Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs

OBJECTIVE: To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA). DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 217 client-owned dogs with clinical and radiographic signs of OA. PROCEDURE: Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15. RESULTS: Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.     

The effect of topical pimecrolimus on keratoconjunctivitis sicca and chronic superficial keratitis in dogs: results from an exploratory study

OBJECTIVE: Pimecrolimus is an ascomycin derivative that interferes selectively with the activation of T cells and mast cells and inhibits the production of inflammatory cytokines. This study evaluated the efficacy of an experimental ophthalmic formulation of pimecrolimus in treating keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs. ANIMALS AND PROCEDURES: Eight dogs with KCS and six with CSK were included. The dogs were of various breeds, suffered from chronic conditions, and had been pretreated unsuccessfully. The affected eyes were treated with 1 drop of an experimental, corn oil-based pimecrolimus 1% formulation three times a day. Parameters evaluated included Schirmer tear test (STT), ocular discharge, conjunctival inflammation, corneal inflammatory cell infiltrate and scarring, and comfort level. RESULTS: The effect of pimecrolimus 1% was pronounced (increase in STT values to higher than 4 mm/min, no signs of inflammation) or moderate (increase in STT values of 3-4 mm/min, mild signs of corneal/conjunctival inflammation) in a total of 6/8 animals with KCS. In 4/6 animals with CSK, the effect was either pronounced (total regression of fibrovascular infiltration into the cornea, no corneal scarring) or moderate (distinct regression of pannus, mild corneal scarring). The response to treatment was unsatisfactory in four of 14 animals. CONCLUSION: Results of this exploratory study suggest that topical 1% pimecrolimus may be a new effective treatment for keratoconjunctivitis sicca and chronic superficial keratitis in dogs.     

Effect of hyposensitization on atopic dermatitis in dogs

In a double-blind study, 51 dogs with clinically defined atopic dermatitis were injected with either alum-precipitated allergen solutions or a placebo. Comparing the treatment results of both groups on the basis of scores for clinical signs, a significant difference in clinical improvement was established in favor of the allergen-treated dogs (P less than 0.01). The proportional changes of scores for clinical signs in the allergen-treated group ranged between +27.3% and -100% (median, -61.5%) and in the placebo group between +36.4% and -100% (median, 0.0%) with respect to the initial scores. Immediate skin test reactivity disappeared only in the dogs with a good clinical response. Of 27 dogs treated with an allergen solution, 16 (59.3%) had an improvement of 51% or more. In the placebo group, 5 of 24 dogs (20.8%) reacted this way. There was total remission of the clinical signs in 9 and 4 dogs, respectively. In the dogs in which, after 9 months of hyposensitization, any improvement was observed, the chance for final improvement of more than 51% was calculated as 84%. Discriminant analysis revealed that evaluation of the effect of immunotherapy can be restricted to the 9-month follow-up examination.     

Clinical trial evaluating the efficacy and safety of cyclosporine in dogs with atopic dermatitis

OBJECTIVE: To determine efficacy and safety of cyclosporine in the treatment of atopic dermatitis among dogs in North America. DESIGN: Randomized controlled (phase 1) and open-label (phase 2) trials. ANIMALS: 268 dogs with atopic dermatitis. PROCEDURE: In phase 1, dogs were randomly assigned to be treated with cyclosporine (5 mg/kg [2.3 mg/Ib], PO, q 24 h) or a placebo. In phase 2, all dogs were treated with cyclosporine for 16 weeks. Frequency of cyclosporine administration was decreased if dogs improved clinically. RESULTS: At the end of phase 1, canine atopic dermatitis extent and severity index (CADESI) scores for dogs treated with cyclosporine were significantly lower than scores for control dogs. Percentage of dogs with severe pruritus decreased from 67% to 16% for the cyclosporine group but from 66% to only 61% for the control group. During phase 2, cyclosporine dosage was decreased to every-other-day administration in 39% of the dogs after 4 weeks. After 12 weeks, 22% of the dogs were treated twice weekly and 36% were treated every other day. After 16 weeks, CADESI score had decreased > 50% in 68% of the dogs and 47% of dogs had no or mild pruritus. The most frequent adverse reactions were gastrointestinal tract signs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cyclosporine is efficacious for the treatment of atopic dermatitis in dogs and that frequency of cyclosporine administration can be reduced following an initial induction period. The drug was well tolerated.     

Safety and efficacy of injectable and oral maropitant,a selective neurokinin1 receptor antagonist,in a randomized clinical trial for treatment of vomiting in dogs

Maropitant (Cerenia?), a selective neurokinin₁ receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two‐hundred seventy‐eight dogs were enrolled from 29 veterinary hospitals. Two‐hundred fifty‐two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant‐ and one placebo‐treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24‐h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly (P ≤ 0.0012) reduced in maropitant‐treated dogs as 50% (32/64) of placebo‐treated dogs continued to vomit compared to only 21.8% (41/188) of maropitant‐treated dogs. Post‐treatment clinical signs were consistent with clinical diagnoses and judged not to be treatment related. In this clinical trial, maropitant was safe and effective in reducing emesis due to various etiologies in dogs.     

Pregabalin alleviates clinical signs of syringomyelia-related central neuropathic pain in Cavalier King Charles Spaniel dogs: a randomized controlled trial

ObjectiveWe aimed to assess the efficacy and benefit-risk profile of pregabalin (PGN) to reduce the clinical signs of central neuropathic pain (CNeP) as reflected by scratching episodes in dogs with symptomatic syringomyelia (SM).Study designRandomized, double-blind, placebo-controlled crossover study.AnimalsA total of 12 client-owned Cavalier King Charles Spaniels (age, 1.1–7.4 years, bodyweight, 8.2–10.8 kg) with magnetic resonance imaging-confirmed SM and clinical signs of CNeP.MethodsDogs were randomized to either PGN 150 mg or placebo for 25 days, followed by 48 hour washout period before crossover to the alternate phase of 25 days. The primary outcome was defined as number of scratching events during 10 minutes of video-recorded physical activity. Treatment effect was estimated using a generalized estimation equation model. Benefit-risk and quality of life assessments were obtained through owner interviews focusing on potential adverse events.ResultsThe treatment effect estimate was an 84% (95% confidence interval = 75–89%) reduction in mean number of scratching events relative to baseline compared with placebo (p < 0.0001). Owner-assessed satisfactory quality of life was status quo and rated as ‘good’ or ‘could not be better’ in six/11 dogs and improved in four/11 dogs. The most prevalent adverse events were increased appetite in nine/12 dogs and transient ataxia in nine/12 dogs. There was one dog withdrawn by the owner 7 days after crossover to PGN owing to persistent ataxia. No dogs needed rescue analgesia during the trial.Conclusions and clinical relevancePGN is superior to placebo in the reduction of clinical signs of SM-related CNeP in dogs. At a dose range of 13–19 mg kg^–1 orally twice daily, the encountered adverse events were acceptable to all but one owner.     

The effect of nematode administration on canine atopic dermatitis

Canine atopic dermatitis is a common disease and is considered as an animal model of the human disease. Immunomodulation by helminths is reported in several species. The aim of this study was to determine whether nematodes have an immunomodulatory effect on atopic dermatitis in dogs. In the pilot study, 12 atopic dogs were infected with either embryonated eggs of Trichuris vulpis (500 and 2500 eggs in 3 dogs each) or L3 larvae of Uncinaria stenocephala (100, 500 and 2500 eggs in 2 dogs each), respectively, for 3 months. Pruritus was evaluated with visual analogue scales and clinical lesions with the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies were obtained for histopathology at the beginning and end of the study. In the subsequent placebo-controlled, double-blinded, randomised study, 21 dogs received either 2500 embryonated T. vulpis eggs or placebo and were evaluated similarly. In addition, allergen-specific serum IgE concentrations were determined. All dogs in the pilot study improved in their lesion scores, most in their pruritus scores. The cutaneous inflammatory infiltrate did not change significantly. In the subsequent randomised study, there was no significant difference between placebo and Trichuris administration in regard to pruritus or CADESI. IgE concentrations also did not change significantly. Infection with T. vulpis did not significantly change clinical signs of canine atopic dermatitis.