Diagnostic Dermatology

History and clinical signs

A 7-year-old, spayed female, English bull terrier was referred to the Atlantic Veterinary College with a 4-year history of progressive seasonal pruritus accompanied by skin lesions that predominantly affected the muzzle, face, and trunk. The clinical signs had worsened each year. The lesions were first noted in the 1st wk of May, continuing through the summer and fall, and resolving by December. The owners felt that there was an association between black fly bites and the dog’s lesions. The owners described the itching as moderate in intensity. Previous therapies included cephalexin (Novolexin; Novopharm, Toronto, Ontario), clavulanic acid potentiated amoxicillin (Clavamox; Pfizer, Montreal, Quebec), loratidine (Claritin; Schering, Pointe Claire, Quebec), prednisone (Novoprednisone; Novopharm), and a sulphur-salicylic acid shampoo (Sebolux; Virbac, St Lazare, Quebec). Some improvement was noted with each of these treatments, but resolution was never attained. At the time of the 1st referral visit in July, the dog was receiving cephalexin (Novolexin; Novopharm), 26.1 mg/kg bodyweight (BW), PO, q24h and a sulphur-salicylic acid shampoo (Sebolux; Virbac) twice weekly.

On presentation, multiple erythematous punctuate lesions measuring 2 to 5 mm in diameter were noted over the muzzle, face, trunk, and all 4 legs. Some lesions were ulcerated and eroded, while others had crusts. Some of the full thickness lesions were draining purulent, serosanguinous material, or both. The dog was moderately pruritic; owners reported that she licked and scratched herself 1 or 2 times/h.

What is your clinical diagnosis and therapeutic plan?

Differential diagnoses for seasonal pruritus, folliculitis, furunculosis, and panniculitis include pyoderma, demodicosis, scabies, fungal granuloma, hypersensitivity disorders (atopy, flea-bite hypersensitivity, insect-bite hypersensitivity, contact hypersensitivity), cutaneous drug reaction, systemic lupus erythematosus, mast cell tumor, and epitheliotropic lymphoma.

Cytologic examination of skin samples, using an impression smear technique, revealed high numbers of degenerative and nondegenerative neutrophils. Skin scrapings were negative for ectoparasites, including Sarcoptic scabei and Demodex canis. Results from a complete blood cell count revealed a mild leukocytosis, characterized by a mild neutrophilia, and mild lymphocytosis. These findings were interpreted as being stress, caused by inflammation, or both, with possible chronic antigenic stimulation. No significant abnormalities were noted on serum biochemical analysis. An antinuclear antibody titer was negative at 1:80.

The histopathologic changes in examined sections of skin varied and correlated with the severity of the gross lesions from which they were obtained. The epidermis and the walls of follicular infundibulae were mildly to moderately regularly thickened and the surface was multifocally ulcerated. In less inflamed areas, the superficial dermis was mildly edematous and contained mild, perivascular to interstitial, infiltrates of eosinophils, lymphocytes, plasma cells, and macrophages. In other areas, denser aggregates of epithelioid macrophages, neutrophils, lymphocytes, plasma cells, and fewer eosinophils were also oriented around hair follicles and adnexal structures. In several foci, inflammatory infiltrates partially to completely, effaced the walls of follicles (Figure 2) and occasionally extended into the underlying panniculus. Hemorrhage and prominent dermal edema were associated with more acute areas of furunculosis, while in more chronic lesions, inflammatory infiltrates were surrounded by dense fibrous connective tissue. The histopathological diagnosis was severe, subacute to chronic, multifocal, pyogranulomatous and eosinophilic, interstitial dermatitis with furunculosis. Although these histologic lesions are relatively nonspecific, in the context of the clinical history, these findings were consistent with a diagnosis of seasonal allergic dermatitis, possibly due to mosquitoes, black flies, fleas, or environmental allergens. The owner was advised to continue with the oral cephalexin and sulfur-salicylic acid shampoo therapy until a revisit in the fall for intradermal testing.

Figure 2.

The image depicts moderate perivascular to interstitial and perifollicular, inflammatory cell infiltrates within the dermis, which in this area surround and partially efface the wall of a hair follicle resulting in furunculosis. Bar = 100 μm.

Intradermal allergy testing revealed marked reactions to horse flies and Culicoides, moderate to marked reactions to black flies and deer flies, moderate reactions to mosquitoes and fleas, and a mild reaction to house dust. The therapeutic plan for this dog included an antibiotic to resolve the ongoing overgrowth of Staphylococcus intermedius, an anti-inflammatory to decrease the exaggerated response to the insect hypersensitivities, minimization of exposure to insects, and supportive care for pruritus. Cephalexin (Novolaxin; Novapharm), 26.1 mg/kg BW, PO, q24h was to be continued for at least 1 mo. Prednisone (Novoprednisone; Novopharm), at 1 mg/kg BW, PO, q24h, was the chosen anti-inflammatory drug as the fly season was reaching its end. This dose was to be tapered gradually over the remainder of the fly season with the intention of discontinuing therapy for the winter. Prophylactic therapy with prednisone was suggested from April until November. It was recommended that the dog stay indoors as much as possible during peak times for flies and that she wear a t-shirt when she needed to be outdoors. Once to twice-weekly shampoo therapy with a benzoyl peroxide shampoo (Pyoben; Virbac) was recommended. A fish-based commercial veterinary diet containing high levels of omega-3 essential fatty acids (Skin Support; Royal Canin, Toronto, Ontario) was also instituted.

Discussion

Insect bite hypersensitivities (IBH) are a growing area of interest in veterinary dermatology (1). The most notable and well- characterized IBH is flea-allergic dermatitis; however, other insect and arachnid induced hypersensitivities are now gaining more attention. Biting insects incriminated in IBH include Tabinidae spp (horseflies, deerflies), Culicidae spp (mosquitoes, gnats), and Simulidae spp (blackflies).

The diagnosis of IBH is generally based on clinical signs and a dermatological examination, with improvement noted after aggressive insect control and prevention of insect bites (2). The diagnostic approach should include ruling out other causes of pruritus, including parasitic dermatoses, dermatological adverse food reaction, and environmental hypersensitivity (atopy). No breed, age, or sex predilection has been noted. Cases may be seasonal or nonseasonal, depending on geographical location and correlated to the presence of biting insects in the local environment. Pruritus is a consistent feature. Lesions tend to involve the thinly haired areas of the body, especially the bridge of nose, muzzle, pinna, groin, and ventral abdomen and legs (1,2). The presence of truncal lesions in this case was likely associated with the short hair coat of the English bull terrier.

The classical description of the lesion is an erythematous maculopapular dermatitis; however, a wide variety of presentations is possible. In some cases, this is likely due to secondary bacterial infection and self-induced trauma. Crusting, secondary alopecia, lichenification, and secondary bacterial pyoderma, including folliculitis and furunculosis are potential findings in chronically pruritic individuals. Nodules and firm plaques can also develop over time. Skin biopsy confirms the presence of a perivascular dermatitis with eosinophil involvement. An eosinophilic dermatitis, affecting the bridge of the nose, pinnae, and footpads, associated with mosquito-bite hypersensitivity has been noted in the cat (3).

Therapy for pruritic lesions secondary to IBH relies mainly on avoidance of insects during peak seasons and time of day, and the use of glucocorticoids (1,2). Additional therapies target secondary pyoderma and utilize various supportive strategies for itchy skin. The use of insect repellents can be considered; however, in the case of very sensitive individuals, they are unlikely to be of significant benefit. Allergen-specific immunotherapy for insect-bite hypersensitivity has not been evaluated in the dog.

Although allergen exposure by biting is an important method, sensitization inhalation and percutaneous absorption of insect and arachnid allergens has been suggested to be important in some cases of atopy (1,4). In a study that took place in the southwestern United States, approximately 50% of the suspected atopic dogs with negative intradermal tests to routine allergens (pollens, molds, flea, and dust mites) had positive reactions to 1 or more insects and arachnids. In a study from the eastern United States, 14% of dogs with negative or weakly positive intradermal tests to routine allergens had positive reactions to 1 or more insect and arachnid allergens (5). Another study from the northeastern United States found that 63% of suspected atopic dogs had 1 or more positive reactions to insects, although none of the dogs had reactions to insects only (6). The case presented in this article is unusual in that the dog had such severe and specific reactions to insect allergens on the intradermal skin test, with only a very mild reaction to a noninsect allergen, namely, house dust.

Cross-reactivity between black fly, black ant, cockroach, and flea has been shown using an ELISA (7). In this case, the strongest reactions were noted to horse flies and Culicoides. Because of the potential for cross-reactivity, we cannot say that they are most important allergens for this dog. Minimizing exposure to all biting insects is an essential part of case management of all patients with severe insect bite hypersensitivity.

Figure 1.

Multiple erythematous crusting, ulcerated and eroded over the muzzle, face, trunk, and all 4 legs of a 7-year-old, spayed female, English bull terrier.