Ciclosporin therapy is associated with minimal changes in calcium metabolism in dogs with atopic dermatitis

Background – Ciclosporin is widely used in the management of canine atopic dermatitis. In humans, ciclosporin therapy has been linked to disturbances in calcium metabolism and resultant skeletal disorders. Objectives – The objective of this study was to assess calcium homeostasis in dogs before and after a 6 week course of once daily oral ciclosporin at the licensed dose (5 mg/kg). Animals – Sixteen client‐owned dogs with spontaneous atopic dermatitis. Methods – Serum concentrations of calcium, phosphate, creatinine, 25‐hydroxyvitamin D, 1,25‐dihyroxyvitamin D and plasma concentrations of ionized calcium and parathyroid hormone (PTH) were measured, together with the urinary fractional excretion of calcium and phosphate. The extent of skin lesions was scored using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)‐03 and the degree of pruritus by the Edinburgh Pruritus Scale prior to and at the end of the study. Results – The CADESI‐03 and the Edinburgh Pruritus Scale scores decreased satisfactorily in all dogs by the end of the study. Plasma PTH concentrations were significantly increased (P = 0.02) following ciclosporin treatment, whereas all other biochemical parameters were not significantly different from their starting values. The increase in PTH was mild in most cases and the proportion of dogs that had a PTH concentration above the reference range was not significantly different following treatment. Conclusions and clinical importance – This study indicates that ciclosporin has minimal impact on calcium metabolism in dogs with atopic dermatitis when used at the licensed and clinically effective dosage for 6 weeks.     

Successful treatment of sebaceous adenitis in a rabbit with ciclosporin and triglycerides

A 4-year-old rabbit was presented with a chronic exfoliative dermatitis and patchy alopecia. General physical examination revealed no abnormalities. Skin scrapings and fungal culture were negative. A blood sample was obtained for a complete blood cell count and biochemical profile, and yielded results that were within normal limits. Radiographic examination of the thorax excluded the presence of a thymoma. Histopathology of the skin showed orthokeratotic hyperkeratosis, absence of sebaceous glands and mural lymphocytic folliculitis, consistent with sebaceous adenitis. Oral treatment was started with ciclosporin dissolved in a medium-chain triglyceride solution (Miglyol 812), combined with essential fatty acids and topical propylene glycol sprays. Within 2 months of treatment, complete regression of skin lesions and regrowth of hair was observed. Serum chemistry values including kidney and liver function tests remained within reference range during the course of treatment. Histopathological examination of control biopsies of the skin showed presence of normal sebaceous glands and active hair follicles. Treatment was changed to a different pharmaceutical formulation of ciclosporin without Miglyol and deterioration of clinical signs was noticed. Using pure Miglyol 812, however, resulted in a gradual improvement of 60%. A nearly complete response was again observed after re-administration of the combination ciclosporin/Miglyol. It is hypothesized that sebaceous adenitis in the rabbit is most likely due to an autoimmune reaction directed at the sebaceous glands and a defect in lipid metabolism. The outcome indicates that a combination of ciclosporin and Miglyol 812 is a promising new treatment for sebaceous adenitis in rabbits.     

Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.     

Oxidative stress markers in canine atopic dermatitis

There are no data in the veterinary literature relating to oxidative stress in canine atopic dermatitis (CAD). The study aimed to determine levels of oxidative stress markers, plasma malondialdehyde (MDA), total antioxidant capacity (TAC), whole blood glutathione peroxidase (GPX) and erythrocyte superoxide dismutase (SOD), in 15 CAD patients and 17 healthy dogs. A correlation between CADESI (Canine Atopic Dermatitis Extent and Severity Index) score and MDA was also determined. Significantly higher plasma MDA levels were found in patients than in healthy dogs. The significant, highly positive correlation determined between CADESI score and MDA in the patient group indicates an association between the severity of CAD and the extent of oxidative damage to membrane lipids. There were no significant differences in TAC, GPX and SOD between patients and healthy dogs. Our findings suggest that oxidative stress with increased lipid peroxidation could be involved in the pathogenesis of atopic dermatitis in dogs.     

Symmetrical alopecia, scaling and hepatitis in a rabbit

A 5-year-old rabbit with inappetence, symmetrical alopecia and skin lesions was examined. No mites or Malassezia were found in skin scrapings and tape impressions and dermatophyte culture was negative. Trial therapy with ivermectin did not reduce skin lesion severity, and euthanasia was performed because of anorexia after 1 month. Histopathology of the skin showed hyperkeratosis, lymphocytic exocytosis, cell-poor interface dermatitis (lymphocytic infiltration and apoptotic cells in basal layer of epidermis), absence of sebaceous glands and lymphocytic mural folliculitis comparable to sebaceous adenitis and thymoma-associated exfoliative dermatitis previously described in rabbits. The liver exhibited an interface hepatitis, comparable to autoimmune hepatitis in man. The occurrence of morphological similarities to exfoliative dermatitis and sebaceous adenitis in rabbits, in association with an autoimmune hepatitis, has not been described before.     

FC-41 A prospective pilot study on the use of cyclosporin on feline allergic diseases

This study evaluated the efficacy of Phytopica^TM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6-week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg Phytopica^TM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention-to-treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n  = 30), 23.4% (200 mg/kg; n  = 29, P  < 0.01), 8.5% (400 mg/kg; n  = 29) and 3.9% (placebo; n  = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P  = 0.038) only in the 200 mg/kg treatment group ( n  = 14). In conclusion, this study demonstrates that Phytopica^TM is an effective nonsteroidal treatment for canine AD.
Funding: Phytopharm plc.     

Thymoma-associated exfoliative dermatitis in a rabbit

A 5-year-old rabbit with generalized scaling is presented. Multiple skin scrapings and acetate tape impressions were negative for mites and Malassezia. Culture for dermatophytes was also negative. Skin biopsies showed similarities with sebaceous adenitis described in rabbits (absence of sebaceous glands, perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, lymphocytic mural folliculitis, interface dermatitis). The owners refused any treatment and 2 months later the rabbit was euthanized due to anorexia. At necropsy a mass was found in the anterior mediastinum. Histopathology confirmed a diagnosis of thymoma. A possible paraneoplastic skin disease was suspected, based on similarities with thymoma-associated exfoliative dermatitis in cats.     

Validation of CADESI-03, a severity scale for clinical trials enrolling dogs with atopic dermatitis

In dogs, atopic dermatitis (AD) is a common and chronic allergic skin disease that often necessitates treatment with pharmacological interventions. In the last 30 years, numerous clinical trials testing the efficacy of anti-inflammatory drugs have been reported, but there has been a lack of consistency in the assessment of outcome measures. Several clinical scales have been employed over time, but none of these scoring systems were ever tested for validity and reliability. A committee of the International Task Force on Canine Atopic Dermatitis evaluated the currently available scales used to assess disease morbidity in humans and dogs with AD, and a third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) was designed. This version was expanded from previous ones by redistribution and increase in body sites tested, the use of an additional lesion reflecting underlying pruritus (e.g. self-induced alopecia) and an increase in the numerical range of severity for each lesion. The CADESI-03 scale was tested for validity and reliability in a cohort of 38 dogs with AD. Overall, this revised version of the CADESI was found to exhibit acceptable content, construct, criterion, and inter- and intra-observer reliability and sensitivity to change. As a result, this scale is recommended as a validated tool for assessment of disease severity in clinical trials testing the efficacy of interventions in dogs with AD.     

FC‐39 Successful management of canine atopic dermatitis using a plant extract: a randomized,double‐blinded,placebo‐controlled trial

This study evaluated the efficacy of Phytopica^TM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6‐week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg Phytopica^TM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention‐to‐treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n = 30), 23.4% (200 mg/kg; n = 29, P < 0.01), 8.5% (400 mg/kg; n = 29) and 3.9% (placebo; n = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P = 0.038) only in the 200 mg/kg treatment group (n = 14). In conclusion, this study demonstrates that Phytopica^TM is an effective nonsteroidal treatment for canine AD. Funding: Phytopharm plc.     

Masitinib decreases signs of canine atopic dermatitis: a multicentre, randomized, double-blind, placebo-controlled phase 3 trial

This study investigated the efficacy and safety of masitinib, a selective tyrosine kinase inhibitor capable of downregulating mast cell functions, for treatment of canine atopic dermatitis (CAD). Dogs with confirmed CAD received masitinib at 12.5 mg/kg/day (n = 202) or control (n = 104) for 12 weeks. A reduction in CAD Extent and Severity Index (CADESI-02) score of ≥ 50% at week 12 was observed in 61% of masitinib-treated dogs versus 35% of control dogs (P < 0.001), according to the modified intent-to-treat population. For dogs resistant to ciclosporin and/or corticosteroids (60% of the study population), CADESI-02 response rates were 60 versus 31%, respectively (P = 0.004). The mean reduction in pruritus score of severely pruritic dogs was 46 versus 29%, respectively (P = 0.045). Furthermore, 65% of owners with severely pruritic dogs assessed masitinib efficacy as good/excellent versus 35% control (P = 0.05). Overall, 63% of investigators assessed masitinib efficacy as good/excellent versus 35% control (P < 0.001). Premature discontinuations from the modified intent-to-treat population (28.2% masitinib versus 26.0% control) were mainly due to adverse events (13.4 versus 4.8%, respectively) or lack of efficacy (12.4 versus 18.3%, respectively). In total, 13.2% dogs presented with severe adverse events (16.0% masitinib versus 7.7% control). Masitinib showed a risk of reversible protein loss, although regular surveillance of blood albumin and proteinuria allowed for discontinuation of treatment while the dog was still clinically asymptomatic. Masitinib proved to be an effective and mostly well-tolerated treatment of CAD, including severe and refractory cases, with medically manageable adverse effects.     

A comparison of the clinical manifestations of feeding whole and hydrolysed chicken to dogs with hypersensitivity to the native protein

Twenty‐six dogs with known adverse food reactions were fed whole chicken for 14 days. From this group, 12 dogs with cutaneous manifestations following exposure to chicken meat were selected and randomly divided into two groups (n = 6). Each group was then fed hydrolysed chicken or hydrolysed soy for 14 days in a blinded crossover design with a 17‐day washout period between each diet. Assessments of a CADESI (Canine Atopic Dermatitis Extent and Severity Index) score and pruritus were performed throughout the entire study, and combined in a global score (GS). Serum was collected weekly for the measurement of chicken‐ and soy‐specific IgG and IgE. Dogs displayed the most severe clinical response when eating whole chicken compared to baseline (P < 0.001). The GS was significantly reduced in 11 of the 12 dogs when fed hydrolysed chicken were compared to those fed whole chicken (3.58 ± 2.81 versus 20.38 ± 14.65, P < 0.01). Serum immunoglobulin G and E responses were variable and did not show relationship with specific dietary exposure.     

The efficacy of a commercial shampoo and whirlpooling in the treatment of canine pruritus - a double-blinded, randomized, placebo-controlled study

Twenty‐two dogs with a history of at least 4 weeks pruritus were studied to determine the effect of whirlpool use on the efficacy of topical therapy with an antipruritic shampoo (Allermyl®, Virbac; Bad Oldesloe, Germany). Dogs in group 1 received initially topical therapy with conventional shampooing (2 mL shampoo per kilogram bodyweight) once weekly for 4 weeks. Dogs in group 2 received the same therapy using a whirlpool (Sanwhirl, Peter Aschauer GmbH; Gräfelfing, Germany). The treatments were crossed between the groups resulting in each dog in groups 1 and 2 receiving both therapies. Group 3 was the control group and was treated once weekly in the whirlpool without any shampoo during the 8 weeks of study. Prior to each therapy, dogs were evaluated by a clinician not aware of the type of treatment using a clinical scoring system (Canine Atopic Dermatitis Extent and Severity Index – CADESI). Owners evaluated the pruritus daily on a visual analogue scale. There was a significant difference in pruritus scores but not CADESI scores after therapy between the control treatment and the conventional shampoo therapy or shampoo treatment in the whirlpool. These results provide evidence for the short‐term benefit of shampoo therapy for canine pruritus.     

Tolerability and clinical efficacy of oral immunotherapy with house dust mites in a model of canine atopic dermatitis: a pilot study

Atopic dermatitis (AD) is a chronic, life‐long disease. In humans, immunotherapy (IT) is the only treatment that can alter the course of AD. Oral IT is appealing owing to the ease of administration and the potential for increased compliance. The purposes of this study were to investigate the tolerability, clinical efficacy and effects on allergen‐specific IgE of oral IT using a canine AD model. Thirteen atopic beagles sensitized to house dust mites (HDMs) were randomly divided into two groups. One group received daily oral doses of HDMs while the other group received vehicle only for 7 months. The investigator evaluating the dogs was blinded to the allocation of treatments. Prior to and after 2 and 7 months of IT, dogs were challenged daily with HDMs for 3 days concurrently, and clinical signs were scored using a modified Canine Atopic Dermatitis Extent and Severity Index (CADESI). Prior to and at completion of oral IT, serum was collected for measurement of allergen‐specific IgE. Oral IT was well tolerated, and no adverse effects were noted. Analysis of variance showed no significant effect of time, group and group × time interaction for CADESI scores. In addition, there were no significant differences in allergen‐specific IgE levels. In conclusion, it appears that oral administration of HDMs is well tolerated in these atopic beagles but that this protocol was not sufficient to induce clinical improvement. Further, longer‐term studies will be necessary to explore the potential of oral IT in veterinary medicine.     

Assessment of a correlation between Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and selected biophysical skin measures (skin hydration,pH, and erythema intensity) in dogs with naturally occurring atopic dermatitis

Atopic dermatitis is a common allergic skin disease in dogs. The aim of this study was to examine the possibility of a correlation between biophysical skin variables: skin hydration (SH), skin pH, and erythema intensity measured in 10 different body regions and both total Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and CADESI measured in a given region (CADESI L). The study was conducted using 33 dogs with atopic dermatitis. The assessment of the biophysical variables was done in 10 body regions: the lumbar region, right axillary fossa, right inguinal region, ventral abdominal region, right lateral thorax region, internal surface of the auricle, interdigital region of right forelimb, cheek, bridge of nose, and lateral site of antebrachum. Positive correlations were found between SH and CADESI L for the following regions: the inguinal region (r = 0.73) and the interdigital region (r = 0.82), as well as between total CADESI and SH on digital region (r = 0.52). Also, positive correlations were reported for skin pH and CADESI L in the lumbar region (r = 0.57), the right lateral thorax region (r = 0.40), and the lateral antebrachum (r = 0.35). Positive correlations were found in the interdigital region between erythema intensity and the total CADESI-03 (r = 0.60) as well as the CADESI L (r = 0.7). The results obtained suggest that it may be possible to use skin hydration, pH, and erythema intensity to assess the severity of skin lesion but positive correlation was only found in < 13.3% of possible correlations and usage of these measures in dogs is limited.     

Environmental and oral challenge with storage mites in beagles experimentally sensitized to Dermatophagoides farinae

This study aimed to investigate whether challenge with storage mites elicited flare ups of atopic dermatitis (AD) in Dermatophagoides farinae sensitized atopic Beagles housed in a house dust and storage mite-free environment. Atopic Beagles were environmentally challenged with 50 mg of Tyrophagus putrescentiae for three days in a row. Clinical signs were scored before, 6 h after each challenge and then every 24 h for a total of 5 days using a Canine Atopic Dermatitis Extent and Severity Index. Four healthy Beagles, negative on serology and intradermal testing for both house dust and storage mites, were used as controls and similarly challenged. A month after environmental challenge, the atopic Beagles were challenged by the oral route (50 mg of T. putrescentiae for three days in a row) and evaluated as described. Analyses of variance (ANOVAs) were used for comparisons between groups and types of challenges. All atopic Beagles developed erythematous pruritic lesions clinically compatible with AD on the face, pinnae, feet and ventral abdomen after both environmental and oral challenge. Control dogs did not develop dermatitis except for mild pinnal erythema in one dog. In the environmental challenge, ANOVA showed a significant effect of time, group, and group x time interaction, with atopic Beagles showing significantly higher scores than the controls. There were no significant differences in clinical scores after oral and environmental challenge in the atopic group. Cross-reactivity between house dust and storage mites could therefore contribute to flare ups of AD in house dust mite allergic dogs.     

FC-38 Efficacy of conjugated linoleic acid and black currant seed oil in the treatment of canine atopic dermatitis: a double-blinded, randomized, placebo-controlled study

The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen-specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL-4, TNF and IL-10 was quantitated using RT-PCR. A mixture of allergen extract and liposome-DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t -test. There were significant improvements in pruritus scores ( P  = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL-4 production decreased significantly ( P  = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis.
Funding: Self-funded.     

Masitinib for the treatment of canine atopic dermatitis: a pilot study

There is an on-going need to identify medications suitable for the long-term treatment of canine atopic dermatitis (CAD). Masitinib mesilate is a potent and selective tyrosine kinase inhibitor of the c-KIT receptor. A strong relationship exists between the SCF/c-KIT pathway and pathogenesis of CAD, suggesting that masitinib may potentially fulfil the above role. This study reports on an uncontrolled pilot study of masitinib in CAD. Masitinib was administered orally to 11 dogs at a mean dose of 11.0 ± 1.83 mg/kg/day (free base) for 28 days. Treatment response was assessed by evolution of clinical appearance according to a modified version of the Canine Atopic Dermatitis Extent and Severity Index (mCADESI), pruritus scale and surface area of lesions. Masitinib improved CAD with a mean reduction in mCADESI of 50.7 ± 29.8% (95% C.I. = 29.4–72.0; p = 0.0004) at day 28 relative to baseline, with 8/10, 8/10 and 4/10 dogs showing improvement of ≥33%, ≥40% and ≥50%, respectively. Improvement was further evidenced by a decrease in pruritus score and the surface area of lesions. No serious or severe adverse events occurred during this trial, although 6/11 dogs presented with mild to moderate treatment related adverse events. There is sufficient compelling evidence to warrant further investigation.     

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.