Update on diagnosis of atopic dermatitis
UPDATE ON THE DIAGNOSIS OF ATOPIC DERMATITIS
Anthony Yu DVM, MS, ACVD
Yu of Guelph Veterinary Dermatology
1460 Gordon Street, Guelph Ontario Canada N1L 1C8
Pruritus one of the most common presenting clinical complaints in veterinary dermatology. It is the first clinical sign to present in dogs with allergic dermatitis, even before erythema, papular eruptions, alopecia and other secondary lesions. Unfortunately, pruritus is not exclusive to atopic dermatitis. Pruritus is also associated with many other skin diseases including infectious, parasitic, immune-mediated, cutaneous manifestation of an internal disease and cutaneous neoplasia, making diagnosis of allergic dermatitis more complicated.
Diagnosis of canine atopic dermatitis (environmental allergies) is made by careful evaluation of the historical information, dermatologic examination and elimination of differential diagnoses. Before embarking on treatment for allergies, be certain to always rule-out other primary or confounding causes of pruritus such as parasitic infestation (Otodectes, Trombicula, Cheyletiella, Sarcoptes, Demodex injai, Lice); microbial infections/overgrowth (Staphylococcus, other bacteria, Dermatophytes, Malassezia, other yeasts); other hypersensitivity disorders (flea bite hypersensitivity, dietary hypersensitivity, allergic contact dermatitis, Malassezia or bacterial hypersensitivity); cornification disorders (metabolic diseases, zinc/vitamin A-responsive dermatoses); neoplastic diseases (epitheliotropic lymphoma, mast cell tumour); and other skin conditions (irritant contact dermatitis, cutaneous drug reaction). A common error in practice is to rely on serologic or intradermal allergy testing to confirm a diagnosis of allergies. As parasitic diseases such as Sarcoptes scabiei can lead to the increased production of non-specific or cross-reactive IgE false positive reactions on the allergy test, it is imperative to rule-out ectoparasites. In general, allergy testing is NOT used to diagnose atopic dermatitis, rather to aid in the identification of environmental allergens to include in immunotherapy treatment sets once all other differentials have been eliminated.
The following step-wise approach to pruritus will help to eliminate non-atopic differential diagnoses before pursuing allergy testing in your patient.
Step 1. Detailed History and physical/dermatologic examination
As per Favrot’s Criteria, most atopic individuals will have an onset of clinical signs starting at <3 years of age with “alesional” pruritus, be mostly indoors, have an excellent response to glucocorticoids, have a history of chronic or recurrent yeast infections. The typical distribution pattern of canine atopic patients includes the front feet, concave surface of the pinnae sparing the ear margins, and have no clinical involvement of the dorsothoracolumbar region. Some of the other common areas included in the Canine Atopic Dermatitis Extent Severity Index (CADESI-04) evaluation of clinical symptoms include the face, ventral abdomen/ inguinal region, axillae, flexor surface of the elbow and hock joint, the skin between the accessory and metacarpal pad, and external ear canals. Predisposed breeds include most purebred dogs including French bulldogs, West Highland White Terriers, Shar Pei dogs, Labrador and golden retrievers and German shepherds. When a patient falls outside of these parameters and pattern of distribution, ruling out other pruritic skin conditions is imperative.
Step 2. Eliminate Ectoparasites
With the advent of isoxazolines, eliminating parasitic diseases including sarcoptic mange, cheyletiellosis, otodectic mange, demodicosis, fleas, ticks, and lice has never been easier. As part of a work-up of any pruritic condition, every patient should receive a course of either Bravecto®, Credilio®, Nexgard® or Simparica® as these are all safe and effective treatments. Treatment of all in-contact dogs and the environment (e.g. DustMiteX, drying bedding at high cotton heat) should be pursued. Oral corticosteroids may be used for short term symptomatic relief of pruritus. If the underlying etiology is attributable to a parasitic infection, a 90% reduction in pruritus should be seen after two weeks, 95% after 4 weeks and 100% after 6 weeks of treatments.
Skin scrapings, both deep and superficial, are still valuable diagnostic tools. A positive skin scrape allows the clinician to focus their efforts on the ectoparasite and postpone potentially unnecessary diagnostic tests including dietary trials, allergy testing and dermatophyte PCR.
Step 3. Eliminate Dermatophytosis
In general, dermatophytes tend to cause more of an asymmetric distribution pattern and are typically not pruritogenic except for Trichophyton mentagrophytes. As dogs are aberrant hosts for T. mentagrophytes (most often found in rodents), the fungal organism generates a foreign body reaction that can mimic the pruritus seen with atopic dermatitis. If not diagnosed, patients may be mistakenly administered glucocorticoids to suppress the inflammation and pruritus, subsequently worsening the patient’s condition. If an asymmetric pattern with easily epilating hairs is noted, submitting samples for Microsporum canis, Microsporum gypseum and Trichophyton mentagrophytes PCR testing is warranted.
Step 4. Eliminate Bacterial infections
Bacterial infections cause inflammation, which in turn results in pruritus. Skin cytology of pustules, crusts and epidermal collarettes will help confirm a diagnosis if bacteria are found engulfed within neutrophils. Skin cytology of staphylococcal folliculitis however, may not be as rewarding because the organisms are found deep within the hair follicle and not as readily sampled. At times, the presence of multifocal areas of alopecia with easily epilating hairs at the periphery in the absence of a positive skin scraping for demodicosis justifies empirical treatment with cephalosporins for a minimum of three to four weeks. If an incomplete response is noted, bacterial culture and sensitivity may be considered, given the increased prevalence of multi-drug resistant bacteria.
Step 5. Eliminate Malassezia infections
Malassezia pachydermatis can be found as a commensal organism in dog’s skin but can also act as an opportunistic pathogen in the right microenvironment. Malassezia causes pruritus by releasing zymogen from the yeast cell wall that activates mammalian complement resulting in inflammation and glucocorticoid non-responsive intense pruritus. As well, Malassezia may elicit a hypersensitivity reaction that results in allergic inflammation, creating an ideal environment for more Malassezia growth, perpetuating a vicious cycle. Keys to diagnosing Malassezia by skin cytology include: 1) aggressive sampling from the skin surface and onto the glass slide as these organisms are keratinophilic; 2) heat fixing the glass slide as Malassezia is lipophilic and hence may be washed off the slide if using the first methanol dip when staining with Diff Quik®; and 3) viewing the slide in a 3-dimensional manner by using frequent fine focus adjustments. Treatment selection is based on correlating Malassezia numbers on cytology with the patient’s clinical signs, especially the intensity of pruritus. One yeast found on cytology in a pet that is intensely pruritic and unresponsive to glucocorticoids, would warrant systemic anti-yeast therapy, including ketoconazole, itraconazole, fluconazole or terbinafine. Topical therapy should be considered in any therapeutic regimen to treat yeast infections and may be considered as the sole treatment modality if client compliance is exceptional. Lastly, Malassezia immunotherapy is another consideration, especially in those patients with adverse reactions to traditional topical or systemic anti-yeast protocols.
Step 6. Rule-out concurrent metabolic diseases
As recurrent bacterial and yeast infections can generate a significant level of pruritus, be certain to eliminate other potential metabolic conditions that may alter a patient’s local immune response including endocrine diseases such as hypothyroidism, hyperadrenocorticism and diabetes. Interestingly, both hypothyroidism and allergies are antibody-mediated diseases to perceived foreign proteins, primarily thyroglobulins in the case of hypothyroidism and allergens in the case of food allergies and atopic dermatitis. Therefore, it is not surprising to find both conditions in the same individual.
Step 7. Eliminate Food Allergies
Although the incidence of pure food allergies encompasses only 10-20% of allergic patients, a combination of both food allergies and environmental allergies are more common. The percentage that each component contributes toward pushing a patient above their allergic threshold varies from patient to patient. A few clues help to determine whether food allergies are a serious consideration including: 1) a history of non-seasonality and steroid unresponsive pruritus; 2) a distribution pattern involving the ears, feet, rears and dorsothoracolumbar region; and if present 3) concurrent gastrointestinal signs (flatulence, vomiting, diarrhea, voluminous bowel movements), respiratory signs (rhinitis, asthma), neurologic (seizures, aggression, attention deficit disorder), or hematologic signs (AIHA, ITP). The only reliable way of identifying these patients at this point in time is by performing a strict elimination diet using a novel or hydrolyzed protein diet, anticipating at least a 50% improvement by 4 weeks and complete resolution of clinical signs by 8-12 weeks. Concurrent use of oral short acting corticosteroids or other anti-inflammatory medication and antimicrobial therapy during the initial phase of a dietary trial may be warranted to help provide immediate relief. Typically, as a positive response is noted to the dietary restriction, medications can be tapered, leaving the diet as the sole treatment modality toward the end of the trial, if food allergy is the primary underlying etiology. Confirming a diagnosis of food allergy is accomplished by controlled dietary challenges every 2 weeks, where a relapse of clinical signs may be noted within 30 minutes to 14 days with the majority of dogs relapsing between 24-48 hours. In general, most dogs react to one or two food antigens; it is uncommon to have a pet that reacts to 3 or more antigens.
Step 8. Eliminate Cutaneous T- Cell Lymphoma
Especially in a patient with a later onset of pruritus that is incompletely responsive to glucocorticoid therapy, a suspicion of cutaneous T-cell lymphoma must be considered. It can mimic clinical signs of atopic dermatitis including the presence of erythroderma and seborrhea and may progress to infiltrative depigmenting lesions including plaques and nodules involving mucocutaneous regions. Skin biopsies, dermatohistopathology and immunohistochemistry will help to confirm the diagnosis.
Step 9. Evaluate the response to a therapeutic trial
Identifying your client’s desires and ability to treat their pet, may dictate that symptomatic therapy would be the ideal course for a patient. With the advent of safe and effective medications such as Atopica®, Apoquel® and Cytopoint®, exposure to glucocorticoids can be minimized. If the frequency and cost of medications are feasible, a client may wish to continue symptomatic therapy for their pet’s atopic dermatitis. However, if the patient continues to require daily therapy year-long, allergen specific immunotherapy is a safer and more cost-effective approach that may result in a decrease or elimination of symptomatic therapy.
Step 10. Pursue allergy testing to identify allergens to include in immunotherapy
If allergen specific immunotherapy is the client’s desired treatment modality, then allergy testing can be performed to identify allergens to incorporate into an immunotherapy treatment set. Serologic and intradermal allergy testing are currently the two readily available methods of identifying a patient’s sensitivities to environmental allergens.
Several laboratories offer regional serologic allergy testing including Heska Corporation (Fort Collins, Colorado), Greer Laboratories (via IDEXX, Lenoir, North Carolina), Biomedical laboratory (Austin, Texas), Spectrum laboratories (Tempe, Arizona), Veterinary Allergy Reference Laboratory (Pasadena, California) and many others. Background (nonspecific) binding, lack of standardization among the various company protocols, allergenic extract preparation, incubation, washing and blocking steps may result in aberrant reactions.
Intradermal allergy testing minimizes false negative reactions by evaluating the local immune response, including locally amplified IgE antibodies that may not make their way into the bloodstream. As well, since not all circulating IgE antibodies make their way from the serum into the skin, intradermal allergy testing minimizes false positive reactions.
Regardless of the testing method, positive reactions should always be interpreted in light of the patient's likelihood of exposure to the allergen and the clinical signs.
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