Treatment Of Canine Atopic Dermatitis Research Articles

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40–60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Preliminary evaluation of a commercial shampoo and fine bubble bathing in the treatment of canine atopic dermatitis: A single-blinded, randomised, controlled study.

Fine bubble (FB) bathing has shown benefits on a mouse model of atopic dermatitis (AD). However, its efficacy in dogs with AD remains to be evaluated. This study aimed to assess the clinical effectiveness of FB bathing in dogs with AD. Seventeen dogs with AD whose clinical presentation showed a Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) score of <40. The dogs were randomly assigned to either the FB bathing group or the shampoo group. The treatments were administered once a week as per the instructions, in a trial totalling 4 weeks. Evaluations were conducted on Day (D)0 and D28 to assess the outcomes of the trial. The severity of AD was measured using the CADESI-04 and the pruritus Visual Analog Scale (PVAS). The skin barrier function parameters, transepidermal water loss (TEWL) and stratum corneum hydration were measured before and after the treatment. Both treatment groups demonstrated a decreasing trend in CADESI-04 scores, yet the FB group exhibited significant improvement in comparison to the shampoo group after 1 month of trial. There were no significant changes in PVAS scores in either group. No significant difference was found in skin barrier function parameters between the two treatments, although TEWL slightly decreased in the FB group and slightly increased in the shampoo group after treatment. These results suggested that FB treatment provides benefits for dogs with AD and offers an alternative topical treatment option with a lesser impact on skin barrier function compared to frequent shampooing.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

Canine atopic dermatitis

This article provides an overview on canine atopic dermatitis, diagnostics and therapeutic options for clinicians in general companion animal practice. Canine atopic dermatitis is a chronic, pruritic, inflammatory and hereditary disease that is seen in around 10% of patients and can require lifetime management similar to eczema in humans. The treatment of canine atopic dermatitis can be separated into reactive and proactive management and should be catered to the patient, owner and the clinical signs exhibited. It is important to effectively communicate with clients to ensure appropriate management.

Canine amniotic membrane-derived mesenchymal stem cells ameliorate atopic dermatitis through regeneration and immunomodulation.

Mesenchymal stem cells (MSCs) are a promising tool for treating immune disorders. However, the immunomodulatory effects of canine MSCs compared with other commercialized biologics for treating immune disorders have not been well studied. In this study we investigated the characteristics and immunomodulatory effects of canine amnion membrane (cAM)-MSCs. We examined gene expression of immune modulation and T lymphocytes from activated canine peripheral blood mononuclear cell (PBMC) proliferation. As a result, we confirmed that cAM-MSCs upregulated immune modulation genes (TGF-β1, IDO1 and PTGES2) and suppressed the proliferation capacity of T cells. Moreover, we confirmed the therapeutic effect of cAM-MSCs compared with oclacitinib (OCL), the most commonly used Janus kinase (JAK) inhibitor, as a treatment for canine atopic dermatitis (AD) using a mouse AD model. As a result, we confirmed that cAM-MSCs with PBS treatment groups (passage 4, 6 and 8) compared with PBS only (PBS) though scores of dermatologic signs, tissue pathologic changes and inflammatory cytokines were significantly reduced. In particular, cAM-MSCs were more effective than OCL in the recovery of wound dysfunction, regulation of mast cell activity and expression level of immune modulation protein. Interestingly, subcutaneous injection of cAM-MSCs induced weight recovery, but oral administration of oclacitinib induced weight loss as a side effect. In conclusion, this study suggests that cAM-MSCs can be developed as a safe canine treatment for atopic dermatitis without side effects through effective regeneration and immunomodulation.

Comparison of whole blood concentrations of oral human generic modified ciclosporin capsules with microemulsified ciclosporin capsules approved for canine atopic dermatitis following a single oral administration to healthy dogs.

There have been no comparative bioavailability studies between the microemulsified ciclosporin formulation, approved for the treatment of canine atopic dermatitis (cAD), and the generic modified formulation of ciclosporin for humans. To compare whole blood ciclosporin concentrations of oral generic modified ciclosporin (Treatment A; Teva Pharmaceuticals) and ciclosporin brand Atopica (Treatment B; Elanco Animal Health) in healthy dogs at 1 and 1.5h following a single oral administration. Whole blood concentrations were evaluated at 1 and 1.5h post-oral administration of treatments A and B in a randomised, blinded, cross-over study with an 8-day wash-out, after a single administration at 4.4-5.3mg/kg/day in eight healthy, male-castrated research beagle dogs. Ciclosporin blood concentrations were measured through the Auburn University Clinical Pharmacology Laboratory. Ciclosporin blood concentrations were below the detection limit before the start of treatment for both groups. Blood ciclosporin concentrations for Treatment A (median 1192 ng/ml) were significantly higher at 1 h post-oral administration than those for Treatment B (median 499 ng/ml; p=0.001). However, no significant differences (p=0.75) in ciclosporin values were observed at 1.5h post-administration between treatments A (median 945 ng/ml) and B (median 809 ng/ml). Generic modified ciclosporin achieved higher blood concentrations at 1h post-administration than Atopica after a single oral administration in healthy dogs; no difference was noted at 1.5h. Further clinical studies using generic modified ciclosporin in client-owned dogs affected with cAD are advocated to confirm its therapeutic efficacy.

The effect of uterine-derived mesenchymal stromal cells for the treatment of canine atopic dermatitis: A pilot study.

Canine atopic dermatitis (cAD) is a common allergic skin condition among dogs that may respond to treatment with mesenchymal stromal cells (MSCs). The aim of this pilot study was to evaluate the safety and efficacy of allogeneic uterine tissue-derived MSCs (UMSCs) for the reduction and control of clinical signs associated with cAD. At two sites, seven client-owned dogs with cAD received two doses of approximately 3.6 x 107 UMSCs given intravenously over 30 min, on Day 0 and Day 14, with monthly clinical follow-up until Day 90 and optional owner phone interview on Day 180. Primary outcomes were pruritus and skin lesions. Pruritus was measured by the owner-assessed Pruritus Visual Analog Scale (PVAS), with treatment success defined as a 2-point reduction in PVAS score at any timepoint after treatment. Skin lesions were evaluated by two veterinarians according to the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). The secondary outcome was safety, which was evaluated via physical exam and hematology, including complete blood count (CBC), serum chemistry, and urinalysis (UA). Treatment was generally well tolerated and associated with a significant reduction in PVAS on Day 30 that was maintained through Day 180. On Day 60, five dogs (71%) achieved treatment success (at least 2-point reduction in PVAS), and three dogs (43%) had a PVAS improvement of 4-5 points. Mean CADESI-4 score was significantly improved on Day 14, Day 30, Day 60, and Day 90, with the lowest mean score observed on Day 60. Three dogs exhibited mild and transient adverse events. These findings suggest that IV-administered allogeneic UMSCs reduce and control clinical signs of cAD, with a durable benefit lasting 3–6 months.

Clinical efficacy ofmembrane-free stem cell extracts for the treatment ofcanine atopic dermatitis.

Despite various treatment options for canine atopic dermatitis (cAD), therapeutic limitations still exist, including adverse effects and low absorption ratios. This study evaluated the effects ofamembrane-free stem cell extract (MFSCE) onthe clinical signs ofatopic dogs. Thirty client-owned dogs previously diagnosed with cAD were separated into placebo (n=10) and MFSCE-treated groups (n=20). The dogs were treated with acream (MFSCE and placebo) via dermal administration twice daily for 14days, and the clinical response was recorded ondays0, 7, and 14. The MFSCE-treated group showed significantly decreased severity ofpruritus onday14 compared tothat onday0. Inaddition, the erythema, pigmentation, skin dryness, and thickness were remarkably decreased inthe MFSCE-treated group onday14 compared tothose onday0 whereas nosignificant changes were observed inthe placebo-treated group. Nogeneral clinical signs oradverse effects were observed inthis study. These results suggest that MFSCE could beasurrogate treatment option for cAD.

Efficacy of Phototherapy With 308-nm Excimer Light for Skin Microbiome Dysbiosis and Skin Barrier Dysfunction in Canine Atopic Dermatitis.

The management of canine atopic dermatitis, an allergic skin disorder, is challenging. To investigate the effect of phototherapy using a 308-nm excimer light as a topical treatment for canine atopic dermatitis, 10 dogs with canine atopic dermatitis and 10 with non-allergic skin were enrolled in this study. Phototherapy was applied every 7 days for a total of 2 months. The skin microbiome, skin barrier function, and clinical outcomes were evaluated after phototherapy. Phototherapy significantly changed the composition of the skin microbiome of dogs with atopic dermatitis and significantly increased the relative abundance of the phyla Actinobacteria and Cyanobacteria. It significantly alleviated the clinical signs of canine atopic dermatitis without serious adverse effects. Transepidermal water loss, as a measure of skin barrier function, significantly decreased after phototherapy. In addition, phototherapy increased microbial diversity and decreased the relative abundance of Staphylococcus pseudintermedius associated with the severity of canine atopic dermatitis. These results suggest that the excimer light therapy is a suitable and safe therapeutic option for canine atopic dermatitis, which is also a spontaneous animal model of atopic dermatitis.

A double-blinded placebo-controlled evaluation of adipose-derived mesenchymal stem cells in treatment of canine atopic dermatitis.

Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis (cAD). Enrolled canine patients were randomly divided into placebo (PBS saline), low-dose (5 × 105 cells/kg), and high-dose (5 × 106 cells/kg) treatment groups. Each patient received three subcutaneous MSCs treatments or PBS saline at four-week intervals with injections at five sites. Patients were monitored by physical exams, pruritus visual analog scales (PVAS) signed by the primary caretaker, canine atopic dermatitis extent and severity index-4 (CADESI-4) scores by two veterinarians, and complete blood count and serum chemistry analysis along with laboratory analysis for potential biomarkers. Patients were kept off any immune-modulating drugs during the study period, and oral antibiotics and topicals were used for managing pruritus and secondary infections. The PVAS scores and the serum miR-483 levels were significantly lower in the high dose group compared to the placebo group at day90 post first-treatment. The CADESI-4 scores of the high dose group also showed downward trends. No severe adverse effects were observed in any patient in this study. The high dose MSC treatment is efficacious in alleviating the clinical signs of cAD until 30days after the last subcutaneous administration of MSCs, and miRNA-483 may be a reliable prognostic biomarker for cAD. The MSCs efficacy and potential biomarkers should be further explored by a larger scale clinical trial.

Ear tip ulcerative dermatitis treated with oclacitinib in 25 dogs: a retrospective case series.

Ear tip ulcerative dermatitis (ETUD) is an uncommon clinical reaction pattern in canine dermatology. The lesions are suggestive of vascular damage which may be caused by inflammatory or noninflammatory diseases, and often are idiopathic. Therapeutic options for ETUD include topical glucocorticoids or tacrolimus, pentoxifylline, vitamin E, doxycycline, tetracycline and niacinamide, sulfonamides, glucocorticoids, ciclosporin and surgical correction. The aims of this retrospective case series were to describe the clinical features and report response to treatment with oclacitinib in dogs with idiopathic, chronic ETUD. Twenty-five privately owned dogs with unilateral or bilateral ETUD. Cases of ETUD which were poorly responsive to conventional therapy and subsequently treated with oclacitinib, are summarised. All cases were tested for leishmaniosis by serological examination [indirect fluorescent antibody test (IFAT) or enzyme-linked immunosorbent assay (ELISA)]. Histopathological examination was performed in two cases. Serological results were negative for leishmaniosis in all dogs. Histopathological changes consistent with proliferative thrombovascular necrosis of the pinnae were documented in two cases. Oclacitinib, used at the standard dose range recommended for the treatment of canine atopic dermatitis, effectively resolved ETUD in 22 of 25 dogs within one to three months. Several of the dogs required prolonged use of twice daily dosing. Oclacitinib should be included among the therapeutic options for ETUD, once infectious diseases have been ruled out.

A proposed medication score for long-term trials of treatment of canine atopic dermatitis sensu lato.

The use of concurrent medications is necessary in trials of treatment of canine atopic dermatitis. Our aim was to use the best available evidence to construct and then to validate a medication score (MS) formula that will estimate the impact of concurrent medications on trial outcomes. Trials of 15 interventions were scrutinized to find those that were consistent in terms of specific medication, administration route and dosage regimen. A MS was constructed in five steps, starting from assigning a score of 1 for each day on oral prednisone, prednisolone or methylprednisolone at 0.5-1.0 mg/kg. The MS score was validated using the clinical records of 35 dogs with atopic dermatitis that had been treated for a period of 12 ± 2 weeks with six of these medications and compared with a previously published non-validated MS. A MS could be assigned to eight treatments, six of which had been administered to the 35 dogs. A positive correlation was seen with the previously published MS and a negative correlation with changes in lesional and pruritus scores. This MS may be a useful tool in new studies evaluating the efficacy of treatments in canine atopic dermatitis.

Experimental Study of Therapeutic Efficacy of the Topical Preparation «Kourochitin» in Skin Allergy

Background: The researchers of PIBOC RAS developed the dermo-protective topical drug called «Kourochitin», active substance of which is known quinazoline alkaloid tryptanthrin. In the present work, therapeutic efficacy of this drug in the treatment of allergic dermatosis was evaluated. Methods: Dermo-protective action of «Kourochitin» was studied in tow murine models: 2, 4- dinitrofluorobenzene- induced allergic contact dermatitis (ACD) and imiquimod-induced psoriasis. Results and Discussion: In a model ACD, it was shown that «Kourochitin» exhibits the curative action on pathophysiological, hematological and immunological parameters in ACD. Namely, «Kourochitin» 1) reduces the level of erythema in the allergen damaged skin area and increases the healing index of the epidermis; 2) normalizes the content of eosinophils, basophils and monocytes in the blood of experimental animals; 3) inhibits the production of main pro-inflammatory cytokines: interleukins - 1 and 2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. In a murine model of imiquimod-induced psoriasis, it was shown that «Kourochitin» application led to reduction in psoriasis severity on the inflamed epidermis of experimental animals. Additionally, in veterinary research, «Kourochitin»-treatment of canine atopic dermatitis almost completely eliminated signs of allergic manifestations on the epidermis. Conclusion: The obtained data suggest that «Kourochitin» as anti-inflammatory, anti-allergic, and wound healing remedy is a potential drug for therapy of various dermatological diseases, in particular allergic skin lesions.

Canine atopic dermatitis: Role of luteolin as new natural treatment.

BackgroundLuteolin has been demonstrated to possess numerous biological effects. However, the effect of luteolin on LPS (Lipopolysaccharides) stimulation in CPEK cells has not been investigated.Hypothesis/ObjectivesAn in vitro model of atopic canine dermatitis was used to identify the antioxidant effect of luteolin as a new treatment that is capable of improving the conditions of veterinary patients.MethodsCPEK cells were treated with or without luteolin in the presence or absence of LPS. A cell viability assay was performed to test luteolin toxicity and the protective effect of luteolin after LPS stimulation. Additionally, enzyme‐linked immunosorbent assay (ELISA) kits were used to detect the levels of IL‐33, IL‐1β, IL‐6, and IL‐8.ResultsLuteolin was capable to significantly decrease levels expression of IL‐33, IL 1β, IL‐6, and IL‐8.Conclusions and clinical importanceLuteolin could be a new pharmacological treatment for canine atopic dermatitis.

A comparative study of subcutaneous, intralymphatic and sublingual immunotherapy for the long-term control of dogs with nonseasonal atopic dermatitis.

Allergen-specific immunotherapy (ASIT) is the only causative treatment of canine atopic dermatitis (cAD). Different routes for administration of ASIT have been used; however, comparative studies are lacking. The present study compared the efficacy and safety of subcutaneous (SCIT), intralymphatic (ILIT) and sublingual (SLIT) immunotherapy. 30 atopic dogs were included and allocation to three groups (SCIT, n=8; ILIT, n=12; SLIT, n=10) was determined by the owners. ASIT was administered using routine protocols. The pruritus Visual Analog Scale (PVAS), canine atopic dermatitis extent and severity index (CADESI), concurrent medications and adverse events were recorded initially and one, three, six and 12 months later. The main outcome measure was return to a normal status, which included CADESI <12, PVAS <2.5 and medication score <10. Drop-outs were distributed evenly and 23 dogs finished the study (SCIT, n=6; ILIT, n=10; SLIT, n=7). Adverse reactions to treatment were rare. At the start of the study, the three groups were homogeneous with respect to clinical signs and concurrent medications. After 12 months of ASIT, the CADESI and PVAS had decreased with a stable medication score in the ILIT and SCIT groups (P < 0.05), while all three scores had increased in the SLIT group. Return to normal state was achieved in one of six (17%) dogs receiving SCIT, in six of 10 (60%) dogs receiving ILIT and in one of seven (14%) dogs receiving SLIT. These findings suggest that SCIT and ILIT improved clinical signs of cAD, whereas ILIT had a much higher return to normal rate.

Pilot evaluation of the oclacitinib sparing effect of oral or topical ceramide products in the treatment of canine atopic dermatitis

Pilot evaluation of the oclacitinib sparing effect of oral or topical ceramide products in the treatment of canine atopic dermatitis

Safety and toxicity of combined oclacitinib and carboplatin or doxorubicin in dogs with solid tumors: a pilot study

BackgroundOclacitinib is an orally bioavailable Janus Kinase (JAK) inhibitor approved for the treatment of canine atopic dermatitis. Aberrant JAK/ Signal Transducer and Activator of Transcription (STAT) signaling within hematologic and solid tumors has been implicated as a driver of tumor growth through effects on the local microenvironment, enhancing angiogenesis, immune suppression, among others. A combination of JAK/STAT inhibition with cytotoxic chemotherapy may therefore result in synergistic anti-cancer activity, however there is concern for enhanced toxicities. The purpose of this study was to evaluate the safety profile of oclacitinib given in combination with either carboplatin or doxorubicin in tumor-bearing dogs.ResultOclacitinib was administered at the label dose of 0.4–0.6 mg/kg PO q12h in combination with either carboplatin at 250-300 mg/m2 or doxorubicin at 30 mg/m2 IV q21d. Nine dogs were enrolled in this pilot study (n = 4 carboplatin; n = 5 doxorubicin). No unexpected toxicities occurred, and the incidence of adverse events with combination therapy was not increased beyond that expected in dogs treated with single agent chemotherapy. Serious adverse events included one Grade 4 thrombocytopenia and one Grade 4 neutropenia. No objective responses were noted.ConclusionsOclacitinib is well tolerated when given in combination with carboplatin or doxorubicin. Future work is needed to explore whether efficacy is enhanced in this setting.

Lokivetmab – uma nova opção para o tratamento e o controle da dermatite atópica canina – revisão

Monoclonal antibodies have been studied in human medicine for a while. They target specific receptors and cytokines, and are highly specific and effective in blocking their target molecule. Lokivetmab is a monoclonal caninised anti-IL-31 antibody that was recently approved for the treatment of atopic dermatitis in dogs. Currently, no other therapeutic monoclonal antibody is used in veterinary medicine. The goal of this review of literature is to updte clinicians on this new biological option for treatment of canine atopic dermatitis.

An attempt to develop guidelines for the diagnosis and treatment of canine atopic dermatitis: current status and issues

An attempt to develop guidelines for the diagnosis and treatment of canine atopic dermatitis: current status and issues

Pharmacokinetics of low-dose methotrexate in healthy beagle dogs.

Methotrexate may be an alternative to ciclosporin in the treatment of canine atopic dermatitis (cAD) as suggested by recent data. The aim of the study was to investigate both the tolerance and the pharmacokinetic behavior of methotrexate (MTX) in plasma, following intravenous (i.v.), subcutaneous (s.c.) or oral (OR) administration over several weeks. Six healthy dogs were given oral MTX once a week, respectively, per dog at 2.5mg/1week, 5mg/4weeks, 7.5mg/3weeks, 10mg/6weeks and 12.5mg/5weeks. No clinically relevant abnormalities of laboratory parameters were noticed. A high inter-individual variation of MTX plasma concentration was observed with a suspicion of saturation phenomenon in absorption. To compare with other routes of administration, six healthy beagle dogs followed a crossover design study at 7.5mg per dog MTX. The absolute bioavailability was 93% for SC injection and 30% for the oral route. The inter-individual variability was quite low following SC administration compared to oral route. Just as in human, given the substantial variability of oral absorption, clinicians cannot assume consistent oral bioavailability of MTX. Therefore, they may consider switching dogs to the SC route in case of absence of clinical response with a weekly oral dose.