Canine allergic dermatitis: Pathogenesis, clinical signs, and diagnosis

In the simplest terms, allergic dermatitis refers to any inflammatory skin disease caused by any type of allergy. The unifying characteristic of these diseases is that they cause pruritus and subsequent inflammation. Depending on the etiology, the event may be short-lived or become a lifelong condition. Table 1 lists the reported allergic diseases of small animals.1,2 These diseases are rarely uncomplicated and often involve secondary infections. Furthermore, more than one core allergic disease is often present concurrently. These factors can make diagnosis and management of allergic dermatitis cases challenging.

This article will focus on atopic dermatitis (atopy, allergic inhalant dermatitis). Other allergic diseases as listed in Table 1 are discussed briefly because they can occur concurrently with atopic dermatitis, must be ruled out before atopic dermatitis is diagnosed, and can be managed using some atopic dermatitis treatment strategies.

Table 1. Allergic Diseases of Small Animals

Hypersensitivity disorders that can cause allergic dermatitis

The clinical signs of all allergic hypersensitivity reactions are similar: pruritus, erythema, hair loss, papules, and, with time, hyperpigmentation and lichenification. Differentiation between the reactions is based on a thorough history, the pattern of clinical signs, and, more often than not, a careful evaluation of likely causes through response to therapy trials.

Urticaria and angioedema. Urticaria and angioedema are classic type 1 hypersensitivity disorders. Clinical signs tend to be acute in onset and include pruritic wheals or large areas of edematous swellings; clients commonly refer to these lesions as hives. Urticarial lesions can be localized or generalized; angioedema tends to be localized to the head. Respiratory distress can occur if the angioedema involves the nares, larynx, or pharynx. Although the cause of urticaria and angioedema is often undiagnosed, triggers may include drugs, vaccines, bacterins, foods, and insect bites or stings. Bacterial folliculitis is frequently misdiagnosed as chronic hives.

Food hypersensitivity. Food hypersensitivity is an adverse reaction to a food or an additive. It occurs in dogs and cats of any age, but in my experience uncomplicated food allergies are most common in pediatric patients and cats. The pruritus is nonseasonal, and it may or may not respond to corticosteroid therapy. The pattern of pruritus and inflammation can be regional or generalized. Secondary bacterial and Malassezia dermatitis and otitis are common. Some animals have concurrent gastrointestinal signs, such as frequent bowel movements, vomiting, diarrhea, or flatulence.

Food hypersensitivity is less common than atopic dermatitis in dogs and cats; however, its true prevalence is unknown because food allergy must be—and rarely is—confirmed by provocative challenge. The increased availability and palatability of novel protein diets make food trials easier to perform because they are more client- and patient-friendly. These diets simplify the diagnostic process in patients with concurrent atopy and food allergy.

Contact hypersensitivity. Allergic contact dermatitis is a rare cause of pruritus in dogs and cats; few well-documented cases exist in the veterinary literature. Clinical signs typically occur in the area where the offending allergen contacts the skin. One of the reasons contact allergies are so rare in small animals is the protective nature of the haircoat. Contact allergies are most likely to occur in thinly haired areas of the body (e.g., ears, perineum, inguina) or in association with topical medication application. Diagnosis can be difficult and is usually made by withdrawing the suspected offending allergen followed by a provocative challenge.3

Flea bite hypersensitivity. Flea allergy dermatitis is the most common allergic skin disease of dogs and cats. Clinical signs can be seasonal or year-round, depending on where the animal lives. In dogs, the classic presentation is a pruritic, papular, crusted eruption over the dorsal lumbosacral area and caudal aspect of the hindlimbs. Alopecia, secondary seborrhea, hyperpigmentation, and lichenification occur in chronic cases. In cats, lesions can occur anywhere, but the typical presentation is miliary dermatitis with secondary excoriations over the neck, dorsal lumbosacral area, caudomedial thighs, and ventral abdominal area.

Tick bite hypersensitivity. Tick bite hypersensitivity reactions are caused by a local immune response to the tick bite. The most common presentation is a focal nodular reaction at the site of the tick bite. A focal area of necrosis is common, but I have seen a range of tick bite reactions. Pruritus, ulceration, and erythema are variable due to differences in the host's immune response to the bite and the stage of the reaction.

Mosquito and insect bite hypersensitivity.The most well-recognized allergic reaction caused by insect bites is mosquito bite hypersensitivity in cats, which is characterized by a severely pruritic, papular, crusted eruption on the face, ears, head, and footpads.2 I have also seen mosquito bite hypersensitivity in dogs characterized by eosinophilic furunculosis of the face and head (Figure 1). Owners often report seeing the dog swarmed by small insects or mosquitoes. Depending on the geographic region, clinical signs can be seasonal or nonseasonal. The lesions tend to be localized to thinly haired areas, and a thorough history usually reveals that the clinical signs coincide with insect hatches. Owners often report that the lesions resolve if the animal is housed indoors.

Figure 1. A dog with insect bite hypersensitivity.

Ear mite hypersensitivity. Otodectes species hypersensitivity reactions are most common in cats. With routine ear mite infestations, pruritus is usually limited to the face, head, and ears, and all stages of mites are easily found. The pruritus associated with ear mite hypersensitivity may also be limited to the head or it may be generalized. Diagnosis of this disease can be frustrating because, contrary to routine infestations, the mites are rarely found. A diagnosis is usually made after observing a positive response to miticidal treatment.

Intestinal parasite hypersensitivity. This is a poorly documented and somewhat controversial hypersensitivity reaction. Various intestinal parasites (ascarids, coccidia, hookworms, tapeworms, or whipworms) may cause pruritus, urticaria, seborrhea, or generalized papular crusted dermatitis.1 Hookworm larvae can penetrate the skin and cause inflammation and pruritus as they migrate. But the pathophysiology of the pruritus caused by internal parasitism is unclear. It could be due to a parasite byproduct, an immune reaction on the part of the patient, or another mechanism. Diagnosis is confirmed by ruling out other causes of pruritus, finding parasites on fecal examination, and observing resolution of clinical signs after parasiticidal therapy.

Hormonal hypersensitivity. This is another poorly documented and somewhat controversial hypersensitivity reaction believed to be caused by reactions to sex hormones. It is unclear if it truly exists in dogs or cats. The clinical signs mimic those of other hypersensitivity reactions and tend to coincide in females with the onset of estrus.1 In males, seasonality does not occur. Surgical neutering is curative.

Bacterial and Malassezia hypersensitivity. Many animals with secondary staphylococcal infection or Malassezia overgrowth are pruritic. The pruritus may be caused by the underlying disease as well as by the allergic response to antigens secreted by these organisms.4,5 Antimicrobial therapy and identification of the trigger that predisposes the animal to overgrowth are the keys to successful treatment.

Atopic dermatitis

Atopic dermatitis is a hypersensitivity reaction to inhaled or dermally absorbed environmental allergens and is a common cause of allergic skin disease of small animals. Practitioners must rule out all of the previously discussed diseases before they can diagnose atopic dermatitis.

Causes and pathogenesis. The development of atopic dermatitis is complex. In dogs, it is a genetically programmed and heritable disease. In cats, evidence suggests that the disease is heritable.6 Canine atopy can develop in any dog, but certain breeds are predisposed, such as terriers and retrievers (Table 2).1,7 Geographic gene pools may affect breed predispositions throughout the world.

Table 2. Dog Breeds with a Predilection for Atopic Dermatitis

The immunologic mechanisms involved in the development of atopic dermatitis are the focus of a great deal of study. Part of the immune response involves an IgE-mediated type 1 hypersensitivity reaction, and it is hypothesized that the pathogenesis also involves a T cell-mediated reaction.7-9 For many years, it was presumed that allergen exposure and sensitization occurred primarily through inhalation, hence the name allergic inhalant dermatitis. Percutaneous allergen exposure is now thought to be an important additional part of the pathogenesis; it leads to a cytokine imbalance and altered T cell-mediated response. Allergens from epidermal exposure become bound to epidermal Langerhans' cells and are presented to T cells. Th2 cells are then preferentially activated and secrete cytokines, triggering allergen-specific IgE antibody production.7-9 When allergens cross-link surface-bound IgE antibodies, mast cells degranulate, and preformed and synthesized inflammatory mediators (e.g., histamine, leukotrienes, and substance P) are released. It is this cascade of reactions that is involved in the production of pruritus and subsequent development of inflammation.

Key features of the historical presentation. The owner will report that the dog is pruritic, or you will deduce this from the history; owners may not consider foot licking and face rubbing to be signs of pruritus.

Uncomplicated atopic dermatitis is a glucocorticoid-responsive disease. However, if marked bacterial and yeast infections are present, glucocorticoid therapy alone may not alleviate all of the clinical signs. Therefore, a history of unsuccessful previous treatment with glucocorticoids does not rule out a diagnosis of atopic dermatitis.

The classic age of onset of clinical signs is somewhere between 7 months and 7 years of age, but most dogs develop clinical signs between 1 and 3 years of age. This historical information may not be available from owners who adopted their dog from a shelter. Also, if a dog has traveled with the owner through many geographic regions, signs of atopic dermatitis may not develop until later in life. I have seen dogs develop clinical signs as early as 3 months and as late as 15 years of age.

Clinical signs may be seasonal or nonseasonal; dogs that initially present with seasonal clinical signs may develop nonseasonal atopy with time. Owners may not be aware of this, but careful review of medical records may reveal the pattern. Breed predisposition is another important historical clue (Table 2).

Key features of the clinical presentation. The hallmark clinical sign the clinician is looking for is pruritus or evidence of pruritus, such as excoriations on the body and face, saliva staining, broken stubbly hairs, and hair lodged between the teeth and gums. However, clinical signs can just include recurrent ear disease, recurrent acral lick granulomas, or perineal pruritus.The primary distribution pattern is ventral (Table 3); however, some dogs have only one or two affected areas (e.g., ears or feet). Lesion distribution also tends to be symmetrical, but it is not uncommon for signs to be worse on one side of the body. The clinical signs of atopic dermatitis can overlap with those of other diseases, including the allergic diseases previously mentioned.

Table 3. Common Clinical Features of Atopic Dogs

Diagnostic approach. Atopic dermatitis is diagnosed based on exclusion of other diseases and characteristic clinical features. The patient must have a compatible history, the clinical signs must fit the pattern described above, and other causes of pruritus must be ruled out. Criteria for diagnosing atopic dermatitis in dogs have been proposed (Table 4);10 however, at no time should these guidelines supersede the clinician's judgment. In my practice, pruritus is the most common owner complaint, and most causes of pruritus fall into one of three categories: parasitic, infectious, and allergic. Again, some patients have more than one concurrent problem (e.g., flea infestation and secondary bacterial pyoderma).

Table 4. Willemse Criteria for Diagnosis of Atopic Dermatitis

The keys to diagnosis are client education and a careful and methodical approach to exclusion of other diseases. Clients are more willing to participate in the process when they have a clear understanding that dermatologic problems are solved more by response to specific therapy trials than by a single diagnostic test. They also want to be confident that the clinician has a diagnostic plan. I find it helpful to give clients a checklist that describes the diagnostic process because it illustrates that the diagnosis is not obvious in most cases (Table 5). This checklist becomes part of the medical record and serves as a quick review of the patient's status in the diagnostic process. It also makes it clear that intradermal or serum IgE testing or food trials are not first line diagnostic tests for most patients.

Table 5. Diagnostic Plan for Pruritus

Indications for intradermal skin testing or serum IgE testing. Intradermal testing or in vitro testing (serum IgE testing) does not answer the question, "Does this patient have atopic dermatitis?" Because these tests only reflect allergen exposure, a positive test result must be compatible with a patient's clinical signs if it is to be considered meaningful. In my opinion, intradermal or serum IgE testing is indicated only in patients with a clinical diagnosis of atopic dermatitis for which immunotherapy is being considered. These patients include:

• dogs that have had clinical signs for a total of six months or more during the year

• dogs with atopic dermatitis of any duration whose pruritus cannot be managed medically

• dogs that cannot tolerate glucocorticoid therapy or dogs with conditions in which glucocorticoid therapy is contraindicated (e.g., diabetes mellitus)

• working aid dogs (these dogs cannot be distracted from their tasks by pruritus or compromised by drugs such as antihistamines or glucocorticoids that can change behavior or have unacceptable adverse effects).

Identifying allergens to avoid is one reason for performing intradermal or serum IgE testing. Although causative allergens may be identified, in practice, few allergens can be avoided; environmental allergens are small and can travel on air currents for miles. At best, clients may be able to remove wool rugs or feathers from their home or install a dehumidifier to control molds. It is my experience that dogs with clinical signs severe enough to be considered for allergy testing almost always need polypharmacy for maximum relief of pruritus and a good quality of life.

Before performing allergy testing, be sure that owners understand that it may take up to one year to see a maximum benefit from immunotherapy, that they therefore should be prepared to commit to at least one year of trial treatment, and that if successful, immunotherapy is usually a lifelong, year-round therapy. Owners should also be informed before testing that immunotherapy alone may not relieve 100% of their pet's pruritus and that many dogs still need some type of pharmacologic support to achieve maximum clinical sign remission.

Much has been written about the pros and cons of intradermal vs. serum IgE testing, and this is well reviewed in many sources.1,7,11,12 Briefly, intradermal testing measures the skin's reactivity to allergens injected intradermally, and serum IgE tests measure the reactivity of IgE antibodies in the blood to a particular allergen. Both tests can be used successfully to prepare immunotherapy formulations. The advantages of serum IgE testing include convenience of a single blood draw, less patient stress, no haircoat clipping, less likelihood of a false negative test result due to drugs or sympathetic nervous system response hormones, widespread availability, and lower cost. Seasonality has not been thought to affect the test; however, this has not been my experience. It is well established that only partial correlation exists between serologic and intradermal testing, and the relevance of this is unknown.11 It is important to remember that normal dogs can have positive intradermal and serum IgE test results.

My practice encompasses both referral patients and primary first opinion patients. After reaching a clinical diagnosis of atopic dermatitis, the decision as to which test to use (intradermal vs. serum IgE) depends on the individual patient and the client's resources and preferences. In most cases in which the patient has not had previous diagnostic testing for allergies, I recommend serum IgE testing. If the patient has had previous serum IgE testing and immunotherapy has failed based on that testing, my recommendation is to consider intradermal testing. In some cases, both tests are performed to identify important allergens.

References

1. Scott DW, Miller JH, Griffin CE. Hypersensitivity disorders. In: Muller GH, Kirk RW, eds. Small animal dermatology. 6th ed. Philadelphia, Pa: WB Saunders Co, 2001:571-650.

2. Medleau L, Hnilica KA. Hypersensitivity disorders. In: Small animal dermatology: A color atlas and therapeutic guide. 2nd ed. St. Louis, Mo: Elsevier, 2006;159-188.

3. Marsella R. Contact hypersensitivity. In: Campbell KL, ed. Small animal dermatology secrets. Philadelphia, Pa: Hanley & Belfus, 2003;202-208.

4. Morales CA, Schultz KT, DeBoer DJ. Antistaphylococcal antibodies in dogs with recurrent staphylococcal pyoderma. Vet Immunol Immunopathol 1994;42:137-147.

5. Farver K, Morris DO, Shofer F, et al. Humoral measurement of type-1 hypersensitivity reactions to a commercial Malassezia allergen. Vet Dermatol 2005;16:261-268.

6. Moriello KA. Feline atopy in three littermates. Vet Dermatol 2001;12:177-181.

7. Mueller RS, Jackson H. Atopy and adverse food reactions. In: Foster A, Foil CS, eds. BSAVA Manual of Small Animal Dermatology. 2nd ed. Woodrow House, Gloucester UK: BSAVA, 2002;125-136.

8. Marsella R. Atopy: New targets and new therapies. Vet Clin North Am Small Anim Pract 2006;36:161-174.

9. Olivry T, DeBoer DJ, Griffin CE, et al. The ACVD task force on canine atopic dermatits. Vet Immunol and Immunopathol 2001;81:143-383. (Note: This entire volume is devoted to an in-depth critical literature review on all aspects of canine atopy.)

10. Willemse T. Atopic skin disease: a review and reconsideration of diagnostic criteria. J Small Anim Pract 1986;27:771-778.

11. DeBoer DJ, Hillier A. The ACVD task force on canine atopic dermatitis (XVI): Laboratory evaluation of dogs with atopic dermatitis with serum-based "allergy" tests. Vet Immunol and Immunopathol 2001;81:277-287.

12. Hillier A, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XVII): Intradermal testing. Vet Immunol and Immunopathol 2001;81:289-304.