Treatment of otitis and food allergy

Unfortunately, it was hardly possible to thoroughly clean the ears or even administer ear drops due to a lack of compliance of the headstrong patient, so that Goliat was given an appointment for ear irrigation under general anaesthesia a few days later. However, even before this detailed examination and treatment, a significant improvement of the signs was noted, which was attributed solely to the change in diet. The swelling had almost completely disappeared and pruritus only manifested itself by an occasional shaking of the head. Thus, after thorough ear cleaning under sedation, no further local therapy was necessary. To avoid having to feed Goliat exclusively with dry food, a wet food version of hydrolysed diet – also based on poultry protein and maize starch (Hill’s z/d®) – was additionally fed after about 6 weeks, when hardly any clinical signs of otitis could be seen. The degree of hydrolysis of this diet was probably insufficient, as otitis externa recurred within a few days. After another change in diet back to solely hydrolysed dry food, otitis was cured again.
One study with dogs allergic to chicken also showed that 40% of patients responded to Hill’s z/d® with significantly increased pruritus, whereas RC Anallergenic® did not cause any worsening of clinical signs in any dog (Bizikova et al., 2016).

Further course

A few weeks later – in early summer – despite strict adherence to the diet, Goliat developed mild pruritus on the ears again, but also on the extremities, in the armpits and on the ventral abdomen. In August, the intensity of pruritus ultimately rose to 8 – 9/10 according to the Pruritus Visual Analogue Scale (PVAS). The skin in these areas showed increasing erythema, moderate alopecia, hyperpigmentation and slight yeast odour (Fig. 2 and 3). Furthermore, moderate, seromucous conjunctivitis was noticed (Fig. 4). As no erosions or crusts were present, a skin impression smear was taken using adhesive tape to check for secondary infections. Microscopically, there was not only plenty of pollen but also accumulations of neutrophil granulocytes as well as cocci and a small number of Malassezia.
The diagnostic assessment of a skin scraping for ectoparasites was not necessary as Goliat had permanently been treated with Simparica® (sarolaner).

Suspected clinical diagnosis

Canine atopic dermatitis (CAD) with secondary infections. Since Goliat was fed exclusively with the highly hydrolysed Anallergenic® diet, it seemed very unlikely that the pruritic symptoms were caused by the food allergy.

Atopy treatment

Goliat was bathed twice a week with a care shampoo containing chlorhexidine (Douxo Pyo®) and, additionally, the skin barrier function was enhanced by essential fatty acids and ceramides. Owing to his strict diet, a spot-on preparation was used (Allerderm®). Although erythema and alopecia improved significantly, pruritus became only slightly better under local therapy. Even a Cytopoint® injection (lokivetmab) could only reduce the itching. Therefore, after taking a blood sample to perform an allergy test for environmental allergens, temporary treatment with prednisolone was started (1 mg/kg per day for 1 week, then 0.5 mg/kg per day).
In combination with regular Cytopoint® injections and continued topical treatment, conjunctivitis was cured after a few weeks and pruritus was improved, but still at a level of 6/10 on the PVAS.

ASIT

Since Goliat had shown a positive reaction in the allergy test to all mites, ASIT was ordered. Prednisolone was tapered before starting desensitisation because in relation to its rather high dosage it did little to improve the pruritic symptoms. ASIT was started according to the treatment plan. Initially, Goliat also got additional Cytopoint® against pruritus. In dogs which do not suffer from pruritus at all after the administration of Cytopoint®, the combination with ASIT would not be recommended, especially at the beginning of treatment. When ASIT is started, it is important that the patients are not completely free of symptoms, because otherwise neither improvement nor worsening of the clinical picture can be seen.
But especially when signs are worsening, it is important to react quickly by adapting the ASIT regimen. As Goliat had never been free of symptoms since the onset of pruritus, Cytopoint® was injected once after the start of ASIT. Even after the end of its duration of action, Goliat did not show any increased itching and after 12 weeks, the only sign of the dog’s allergy were short phases of paw licking, especially in the evening before going to sleep (2 – 3/10 PVAS).

Long-term management

Shampoo therapy was reduced to once a week, the weekly administration of Allerderm® spot-on was continued as well as the permanent administration of Simparica®. Goliat is still fed with RC Anallergenic®. To reduce mite pressure in the environment, every week, all sleeping places are washed at 60 °C and dried in the dryer.
Nevertheless, particularly in late summer, Goliat keeps suffering from phases of increased pruritus. However, so far, these phases could be controlled without the use of systemic anti-pruritic medication by more frequent shampooing and the additional application of skin-calming foam (Douxo Calm®).
This “seasonal” worsening of someone suffering from mite allergy can be explained by the fact that house dust mites can multiply exponentially under certain climatic conditions and, thus, allergen load rises sharply. Another possible explanation could be that Goliat now does show a reaction to pollen from late flowering plants, which was not yet visible in the first allergy test. Therefore, another allergy test on seasonal allergens is planned.

Discussion

CAD affects about 10% of the worldwide dog population and is, hence, a common disease. Depending on the study, 3 – 30% of affected dogs suffer from atopic dermatitis and a food allergy at the same time, as is the case with Goliat.
Pathogenesis of CAD is multifactorial: On the one hand, there is a genetic predisposition, but on the other hand, environmental factors also influence the occurrence and the course of CAD. Some breed predispositions are known (e.g. Labrador, Golden Retriever, WHWT, Bullterrier …) – i.e. Goliat as a mongrel should actually carry a lower risk of developing an allergy.
Environmental factors influencing allergies in dogs have been investigated in various studies, with some of them showing contradictory results. One risk factor identified in almost all studies is living or growing up in an urban environment. The hygiene hypothesis postulated in human medicine, which states that high exposure to microbes in childhood protects against allergic diseases, is also likely to apply to veterinary medicine. Other protective environmental factors are: a rural environment, a lot of time in nature, several animals in the household, home-cooked food during pregnancy and separating puppies late from their mother. Negative risk factors, on the other hand, are a very clean environment and lying on upholstery or in places with a high density of house dust mites. Since nothing is known about Goliat’s early history, to some extent, assessing his risk factors is not possible.

Another risk factor that has recently been studied in human medicine is the use of gastroprotective medication (Jensen-Jarolim et al., 2019). In a large-scale retrospective study, it was shown that especially the use of proton pump inhibitors doubles or triples the risk of allergic symptoms requiring anti-allergic therapy. Not only do the drugs have a direct effect on the immune system, but human medicine has also demonstrated a change in the oral and gastrointestinal microbiome, which creates a pro-allergic environment and promotes the development of allergic diseases. For the past few years, intensive research on the importance of the microbiome has also been conducted in veterinary medicine. First results suggest that the gastrointestinal microbiome may influence the development of obesity, allergic dermatitis and neoplasia as well as cognitive functions and renal function. The development of Goliat’s allergies may have been promoted by the treatment of Helicobacter with pantoprazole.
The case of Goliat shows that not every allergy sufferer responds equally well to the classic treatment options and that an individual, often multimodal management is necessary for each patient. ASIT is an important and effective component of it.

Dr. Maria Christian

Clinical examination

The dermatological examination revealed the presence of moderate to mild erythema on the muzzle, axillae, and abdomen. The interdigital and palmar areas of the front paws showed a moderate erythematous and exudative dermatitis. Between toes 3 and 4 of the front paws, there was mild alopecia with a moderate erythematous dermatitis. On the rear paws, the plantar area had mild erythema. The inner surface of the ears, as well as the entrance to the external otic canals, were erythematous. At otoscopy, both ear canals were moderately erythematous, stenotic and the eardrum was only partially visible.

In 2010, the Favrot criteria, with reasonable specificity and sensitivity for the clinical diagnosis of canine atopic dermatitis, were published. These criteria are based on the animal‘s clinical history and dermatological examination.

These criteria are:

• The appearance of the first clinical signs before three years of age
• Animals living mostly indoors
• Corticosteroid-responsive pruritus
• Primary pruritus, without lesions at the beginning of the process (pruritus sine materia)
• Chronic or recurrent yeast or bacterial infections
• Chronic or recurrent otitis externa
• The affection of front feet and ear pinna
• Non-affected ear margins
• Non-affected dorso-lumbar area.

At Rocky, most of the criteria were met.

Diagnostic tests

Cytology
Impression smears were taken from the muzzle, axillae, and abdomen. No bacteria or Malassezia were detected.

Cytology of the ears revealed the presence of neutrophils and cocci bacteria in moderate numbers.

Scotch tape cytology were obtained from interdigital and inter-pad spaces. Malassezia was detected on the tape.

In patients with chronic pruritus, sarcoptic mange is one of the differential diagnoses. However, Rocky received Bravecto® regularly and no other tests (superficial skin scraping) were performed.

Diagnostic and therapeutic plan

Treatment of Malassezia pododermatitis was started with baths with Malaseb® shampoo. External otitis was treated with Aurizon® ear drops (marbofloxacin, clotrimazole and dexamethasone) once a day for 14 days.

An elimination diet is the standard gold test for the diagnosis of food allergy. Rocky was not responding to the horse meat and potato elimination diet he was receiving. Although the diet was designed with a unique novel protein, and a unique carbohydrate source, there could be a cross-reaction problem between feed ingredients or diet errors (such as licking of dishes, eating food crumbles on the ground, or wrong food administration by other people). Therefore a second strict elimination diet with hydrolyzed feed (Anallergenic® of Royal Canin) was proposed for another eight weeks.

Prednisolone was tapered off from the fourth week of the elimination diet (the first week every two days, the second week every three days and then stopped). No improvement was shown under the new elimination diet, and a food allergy was excluded. A serological test for environmental allergens was performed.

Environmental allergen tests

Serology allergy tests are a reliable method to identify relevant environmental allergens for allergen-specific immunotherapy (ASIT) formulation. Dust and storage mites and pollens of grasses, herbs, and trees are the most common environmental allergens. But also, other allergens such as mould spores, insects and epithelia or feathers of animals can cause atopic dermatitis.
To perform an allergen test, the patient must not have received glucocorticoids for at least 12 weeks for injectable depot preparations, 6-8 weeks for oral administration, or 2-4 weeks for topical formulations (ear drops, creams, sprays). To avoid relapse of clinical allergy signs after the withdrawal of prednisolone and the elimination diet, Rocky received Lokivetmab (Cytopoint®) every four weeks.
According to the literature, Lokivetmab does not negatively influence allergy test results. Four months after prednisolone withdrawal, Rocky was tested against perennial, seasonal, epithelial, and animal feather allergens. The results of all the tests were negative. In animals with a clinical diagnosis of atopic dermatitis and negative result in one type of allergy test (serology or intradermal test), the employment of the other methodology is indicated. Rocky‘s intradermal test was also negative.

Diagnosis

Atopic-like Dermatitis (ALD)

Treatment

As the identification of allergen-specific IgE is not possible in atopic-like dermatitis, it is not feasible to formulate an ASIT in such patients. Hence, active and proactive therapy with anti-pruritic drugs like Prednisolone, Apoquel®, Cyclosporine and Cytopoint® is the only possible therapy plan.
Rocky was treated with Apoquel® 16 mg 3/4 tablet every 24 hours (every 12h during the first 14 days). Besides, 1ml of Cortavance® spray (hydrocortisone aceponate) was applied weekly to both ears and also to the skin as proactive therapy.
Although possible skin atrophy with Cortavance® is significantly less likely than with other corticosteroids, the skin should be monitored regularly.
Shampoo therapy was prescribed 1-2 times a week, and Bravecto® every three months was recommended.
To protecting the skin barrier, topical essential fatty acids (EFAs) were applied after the baths. The pruritus was under control with a level between 1-3 out of 10. Periodic rechecks were carried out at least every three months to assess the course of the disease, and the possible appearance of secondary infections.

Discussion

ALD is a pruritic inflammatory skin disease with the same clinical signs as atopic dermatitis, however no allergen-specific IgE against environmental allergens are identified in serology, and the IDT also does not react.
This condition has been known in human medicine for a long time. Atopic dermatitis in human medicine has been divided into intrinsic atopic dermatitis (IAD) and extrinsic atopic dermatitis (EAD). Like dogs with ALD, IAD patients do not show any IgE in serology tests or reaction in the prick test. The prevalence of IAD in human medicine is 10- 45% of cases, that of ALD is described in veterinary literature as 14-25%. Due to the lack of allergen-specific IgE positivity, it is not possible to formulate ASIT in these patients. In the human medical literature, it has been reported that IAD patients can produce allergen specific IgE at a later point in time, but this is still unclear in veterinary medicine. It is therefore uncertain whether it really would make sense to repeat the test at a later point in time.
Rocky showed an excellent response to anti-pruritic treatment (glucocorticoids, oclacitinib, Lokivetmab). There is no clear information on which is the most successful therapeutic approach in patients with ALD. Cyclosporine (CsA) has shown good efficacy in two studies and not shown a good success rate in other reports. To date, no studies have been published about the effectiveness of other drugs in ALD. Little is known about ALD in veterinary medicine, and the diagnosis can be challenging for veterinarians.
In patients with negative allergy test results, it is essential to rule out other pruritic dermatoses such as ectoparasites, food allergy, flea saliva allergy and to adhere to the withdrawal period from medication such as, e.g. Glucocorticoids. Not knowing previous treatments, incorrect test timing or insufficient waiting times for medication are the most common causes of negative allergen test results, which can lead to an over diagnosis of ALD. Therefore, an accurate medical history and proper dermatological examination are needed to avoid incorrect diagnosis.

Amir Davoodi

The development of the disease depends on the individual’s immune response. A cellular or Th1 response would be protective controlling the parasite at the entry point, while excessive antibody production in the absence of a cellular response would induce disease development.

Hass presented an unusual form of leishmaniosis with a papular cutaneous process in the absence of systemic signs of disease. Presence of leishmania amastigotes in skin biopsy diagnosed the infection, indicating the direct participation of the parasite in the inflammatory reaction causing the dermatological condition. The systemic involvement must always be assessed by complementary blood tests: haematology, blood biochemistry, leishmania serology and protein electrophoresis.

Papular dermatitis has been described as a benign cutaneous condition of leishmaniosis in animals with a good cell-type response. It is usually associated with low antibody titer, absence of alterations in protein electrophoresis and proper response to treatment. Probably, in this case, the late diagnosis of the process and the successive treatments with glucocorticoids favoured the dissemination of the parasite and a deviation to a humoral type immune response with antibody production and electrophoresis alteration. However, at the time of diagnosis, no general clinical signs of disease were detected.

It is essential to define the clinical stage of the disease to give a prognosis and establish the most appropriate treatment. Four clinical stages are described: mild, moderate, severe and very severe, depending on the clinical picture and the clinicopathological findings. In this case, the disease was classified as stage II, or moderate, based on the presence of skin lesions, clinicopathological alterations (hypoalbuminaemia and hyperglobulinaemia) and a high titer of anti-Leishmania antibodies.

The treatment was adapted to the indications of the Leishvet Guide and the ESCAPP which establishes the use of Allopurinol (10 mg/kg every 12 h PO) + Glucantime® (100 mg/kg every 24 h for 4 weeks).
The response to treatment was excellent with complete resolution of the lesions and normalisation of the proteinogram. Four years later the dog is still healthy and the leishmania titer converse is negative (Fig. 5).

Dr Carmen Lorente Méndez, DVM, PhD, DipECVD. EBVS® European Specialist in Veterinary Dermatology

Laboklin offers food allergy tests for the detection of allergen-specific antibodies (IgE and IgG) to various food components. The serological allergy test identifies those allergens to which antibodies have been formed (allergen-specific IgE and IgG antibodies to various food components, ELISA). In addition to the “basic” food allergy test, we have also been offering an “extended” and a new “exotic” food allergy test for some time now. This enables you to specifically test these components and then use them for the self-prepared as well as the commercial elimination diet (Tab. 1).

The group of Prof. Dr. Ralf Müller presented a study of the Small Animal Clinic of the University of Munich which showed that the negative predictive value of this test is 81.1% when both antibodies (IgE and IgG) are taken into account (Bethlehem et al., 2012). This means that by feeding food components that tested negative in both antibody classes, the correct elimination diet is used in 4 out of 5 dogs.

This also confirms that food-specific antibodies are useful for selecting the components of an elimination diet due to their high negative predictive value. The owner’s compliance with carrying out the diet is greatly enhanced by a positive test result, specific nutritional suggestions based on it.