Canine atopic dermatitis: report of ten cases

Canine atopic dermatitis (cAD) is a multifactorial allergic disease associated with immune dysfunction and an abnormal skin barrier. Together, these factors result in cutaneous inflammatory and infectious processes with different injury patterns. The clinical understanding and diagnosis of these patterns are crucial for the best clinical management of the atopic patient. As it is often a clinical challenge for the veterinarian, the objective of the present study was to describe the follow-up of ten cases of canine atopic dermatitis. Therefore, a retrospective analysis of ten dogs diagnosed with cAD was performed, from crisis control therapy to maintenance therapy. Dogs received an individualized treatment approach based on their different clinical manifestations. All selected dogs showed an adequate response to the proposed treatments, which provided control of the inflammatory and pruritic stimulus. From the above, it was concluded that canine atopic dermatitis has different clinical patterns and, therefore, individualized therapeutic strategies should be adopted for a better clinical resolution.


Introduction
Canine atopic dermatitis (cAD) is characterized as a clinical inflammatory syndrome whose development involves the interaction between genetic and environmental factors (Marsella, 2021). Together, these factors are able to influence the skin immune response to a pro-inflammatory state, which ultimately leads to microbiome imbalance and cutaneous injuries (Stefanovic et al., 2021).
Pruritus is the main clinical manifestation of cAD, which precedes other clinical signs. The body points commonly affected are distal extremities and areas of limb flexures, face, abdomen and ears (Favrot et al., 2010). Atopic dogs may also present with a variety of lesions, such as erythema, alopecia, excoriations, hyperpigmentation and lichenification (Eisenschenk, 2020). Bacterial infections, most commonly by Staphylococcus pseudintermedius, and fungal, most commonly by Malassezia spp., are common in cAD (Nutall et al., 2019), since the failure of the epidermal barrier favors the exacerbated proliferation of microorganisms residing in the integument. These infections result in a worsening of skin lesions with progression of pruritus and the inflammatory process (Rodrigues-Hoffman et al., 2014).
There are no diagnostic tests for cAD (Marsella, 2021), being it dependent on clinical analysis and sequential exclusion of other pruritic skin diseases (Nutall et al., 2019). Differential diagnoses, ranging from ectoparasites to neoplasms, should be excluded based on anamnesis data, clinical and laboratory findings (Hensel et al., 2015). The first step involves eliminating fleas and ticks, which may be causing the allergic process. In addition, attention should be drawn to other possible ectoparasites, such as some mites, which may be triggering pruritus (Nutall et al., 2019). The next step involves food restriction, with changing of the diet protein source for at least eight weeks . If pruritus is still present, even after completion of all steps, the possibility of canine atopic dermatitis can be considered as a definitive diagnosis (Hensel et al., 2015).
After diagnosis, an adequate therapeutic plan should be established, since cAD has no cure (Marsella, 2021). The treatment aims to improve the quality of life of the animal, as well as the tutor, by minimizing the frequency and intensity of allergic crises (Nutall et al., 2019). Because it is a disease with a complex involvement of the immune system, the treatment must be individualized and based on the dog clinical profile (Eisenschenk, 2020) and, often, it becomes a clinical challenge for the veterinarian. Thus, the objective of the present study is to describe the follow-up of ten cases of atopic dermatitis with varying lesion patterns.

Methodology
The present study comes from a retrospective analysis of cases treated at a private clinic in Fortaleza/CE in the year 2021. Ten patients with a definitive diagnosis of cAD were selected, who were able to follow all stages of care, from suspicion to the diagnostic conclusion. All dogs underwent clinical and dermatological evaluation and the diagnosis of cAD was established after screening and exclusion of other pruritic skin diseases (Nutall et al., 2019). In addition, animals with pruritus without lesions and clinical lesions suggestive of Superficial Pyoderma, Otitis Externa and/or Skin Malasseziosis were included in the present study. Such dogs were submitted, during the clinical-dermatological evaluation, to cutaneous and auricular parasitological and cytological exams in order to confirm and/or exclude skin infections.

Diagnosis of Canine Atopic Dermatitis
Dogs were diagnosed with cAD based on compatible clinical history and exclusion of other pruritic skin diseases. The dogs were also submitted to an elimination diet to evaluate food hypersensitivity and adequate control of ectoparasites to eliminate allergy to flea and tick bites. In addition, parasitological tests were carried out to identify mites, and skin cytological tests to analyze the presence of cutaneous infection at the time of consultation.

Cutaneous and auricular parasitological analysis
The cutaneous parasitological analysis was performed with skin scraping using a scalpel blade. Five random lesions were chosen and, from these lesions, skin material was collected to exclude parasitic diseases. Regarding the auricular parasitological evaluation, this was performed using a swab, which was introduced into the vertical canal in order to collect auricular secretion. This material was placed on a glass slide and evaluated under an optical microscope to exclude ear mites.

Cutaneous and auricular cytological analysis
Aiming at characterizing the cutaneous and otological infectious processes, biological samples from these sites were collected at the time of the clinical consultation. Skin samples were collected from epidermal collars, pustules or skin secretions by scarification and imprinting, while ear secretion samples were collected with a swab. These materials were fixed on microscope slides, stained with Quick-Diff and evaluated with the aid of optical microscopy to identify the microorganisms associated with cAD.

Treatments and clinical follow-up
The animals were initially treated according to clinical-dermatological evaluation. When necessary, immunomodulators, skin barrier replenishers and oral/topical antimicrobials were used, according to previously published studies . Therapy was divided into two stages: flare treatment (day 0) and maintenance treatment (day 30).
The used drugs in each animal are shown in Table 1. Cytopoint (SC) and bathing with Allermyl Glyco Shampoo (2x/week).

Results
The individual data of dogs, as well as the lesion distribution are described in table 2. In the evaluated atopic animals, inflammatory and/or infectious alterations were observed in the ears, limbs, axillae/thorax, groin/abdomen, chin/neck, dorsum, periocular and flank. It is noteworthy that some animals had more than one affected site simultaneously.
Fifty percent (n=5/10) of the dogs were diagnosed with concomitant superficial pyoderma (Figure 1), while 30% (n=3/10) were diagnosed with cutaneous Malasseziosis (Figure 2). Otitis externa (Figure 3) was diagnosed in 50% (n=5/10) of the dogs affected with cAD. Yeasts were the microorganisms most frequently identified on cytological examination (three dogs), followed by coccoid bacteria (two dogs) and rods (one dog). The results are described in Table 2 and the cytological images are shown in Figure 4. Some dogs presented only an inflammatory process, without associated infection.
Regarding the treatment, good clinical resolution of the inflammatory and pruritic process was observed in all animals within a period of 30 days of therapy. After the initial approach, maintenance treatment was carried out, consisting of moisturizing products and skin barrier replenishers, as well as immunomodulators. The individual therapeutic approach is shown in Table 1, and the results of the therapies are shown in Figures 1, 2 and 3.

Discussion
The present study brings a contribution about the clinical follow-up of dogs affected by atopic dermatitis in a private clinic in Fortaleza, with ten different cases of cAD with different clinical presentations. Dogs affected by the disease were mostly adult animals, which is the most common age at which signs associated with cAD appear (Favrot et al., 2010).
Regarding the lesion sites, these are compatible with the disease pattern, being the abdomen, limbs and ears the most affected sites (Favrot et al., 2019). However, lesion sites can also vary according to secondary infections (Bloom, 2014) and to the breeds, a fact that can be attributed to the racial phenotype (Wilhem et al., 2011).
It is also known that in observed lesions there may be disordered growth of microorganisms, since the skin microbiota of atopic animals is altered (Rodrigues-Hoffman et al., 2014). This dysbiosis predisposes to cutaneous infections and triggers abnormal inflammatory responses involved in pathogenesis of atopic dermatitis (Gallo & Nakatsuji, 2011). Such infections can affect both the skin and the ears, being manifestations that make it difficult to resolve the cutaneous inflammation associated with cAD, as they promote an immune polarization towards the Th2 pathway with consequent production of pro-inflammatory cytokines (Pucheu-Haston et al., 2015). In the described animals, the presence of infectious processes in skin and ears was observed, which, when controlled, resulted in the reduction of the cutaneous inflammatory process. It is also noteworthy that such infections are sometimes recurrent, due to the complexity of the relationships between microorganisms and the host (Rodrigues-Hoffmann et al., 2014), and control strategies are needed in order to delay their appearance.
The therapy of cAD involves the combination of several treatments, since it is a pathology of multifactorial etiology and complex pathogenesis, still to be fully understood (Marsella, 2021). Interventions with oral glucocorticoids, oclacitinib, lokivetmab or cyclosporine are part of the therapeutic protocol to promote pruritus relief (Olivry & Banovic, 2019;Marques et al., 2021). Corticosteroids are the first line of widespread antipruritic and anti-inflammatory drugs to control the disease, due to their low cost and high efficacy . After this initial period of therapy, it is recommended to reduce the dose and frequency of drug administration, as well as replacement with therapies with less potential for side effects Olivry & Banovic, 2019). As recommended for human atopic dermatitis (Wollenberg et al., 2018), the drugs were chosen based on the lesion type and intensity.
In infection cases, topical and/or systemic antimicrobials (antibiotics and/or antifungals) should also be used . For the control of bacterial infections, the use of topical antiseptics, such as chlorhexidine, is recommended, and, in refractory cases, the use of systemic drugs, such as beta-lactams and quinolones (Bloom, 2014). Chlorhexidine is an antiseptic that has action against fungi, viruses and most bacteria that cause skin infection, in addition to having residual activity by adherence to the surface of the skin and hair (Ferreira et al., 2019;Larsson & Lucas, 2020). Aiming at the control of fungal infections by yeasts, the use of sulfur, salicylic acid, coal tar or azoles derivatives is recommended (Larsson & Lucas, 2020). In the animals of the present study, topical antimicrobial strategies were adopted, and the use of oral drugs was recommended only in situations of greater lesion severity. This decision was adopted due to the secondary characteristic of infectious processes in cAD (Bloom, 2014), so that oral antimicrobials could potentially destabilize the general microbiota, without guarantees that there will be no recurrence of skin lesions.
With regard to maintenance therapy, the importance of preventing or delaying the onset of the skin inflammatory process is highlighted (Olivry & Banovic, 2019). Therefore, a multimodal therapeutic approach is necessary Bensignor & Videmont, 2022) and, considering the individuality of each patient, the combined use of drugs can be evaluated. It is noteworthy that, as it is a chronic disease (Marsella, 2021), affected dogs undergo long-term treatments  and, therefore, organic monitoring is recommended in order to avoid serious side effects associated with the systemic drugs. In the described cases, different strategies with and without the use of systemic immunomodulators were proposed, based on the intensity of the lesions and pruritic crises of the patients. We also emphasize the importance of therapies aimed at improving the quality of the skin, with the use of moisturizing and skin repair products, so that their use may reduce the severity of subsequent inflammatory crisis.
Auricular therapy involved controlling the infectious and inflammatory process with the use of topical antimicrobials and anti-inflammatory drugs associated with Tris-EDTA. This compound is capable of damaging the cell wall of bacteria, is well tolerated and non-ototoxic (Boyd et al., 2019). As maintenance, neutral cerumenolytic solutions or those incorporated into topical corticosteroids were chosen, in order to constantly control the inflammatory process and, therefore, avoid changes related to chronic inflammation (Huang et al., 2009). Only one out of ten patients had to opt for the continuous use of auricular antimicrobials, since only the control with the previously used topical corticosteroid was not enough for the adequate maintenance of otitis externa crisis.
In this study, all patients presented excellent therapeutic results in the control phase of the pruritic crisis and in the maintenance phase of the treatment, with an improvement in their quality of life, as well as that of their owners. In patients with greater intensity of injury, follow-up was recommended every three months for monitoring and treatment adjustments, and for the others, a visit between four to six months was recommended. The maintenance period of therapy is essential to avoid severe itching (Olivry & Banovic, 2019). However, the difficulty reported by tutors to create and maintain the product administration routine and reassessment consultations is known (Spitznagel et al., 2021). As strategies to improve the adherence of tutors to treatments in the reported animals, the importance of each drug was demonstrated, as well as the correct use of otologic drugs. In addition, it was decided to minimize the number of used drugs, making the routine of drug administration less complex.

Conclusion
From the above, it is concluded that canine atopic dermatitis has different clinical presentations and, thus, different therapies can be adopted in order to culminate in pruritus and inflammation control. It is also important to identify the lesion patterns of this disease, aiming at a more accurate diagnosis, since other differential diagnosis can mimic atopic dermatitis clinical signs.