Stephen D. White, DVM, DACVD
The eosinophilic granuloma complex (EGC) in the cat actually consists of three controversially similar diseases. Despite the name, not all manifestations of this group of diseases always have granulomas. A recent report documented the presence of eosinophilic degranulation products coating but not altering the collagen in all of these disease (1).
These diseases are best thought of as inflammatory reactions of the skin, and may be associated with hypersensitivity diseases. Thus, while this "complex" has generally been regarded as "idiopathic", the veterinarian should attempt to search for any underlying diseases. [A recent article (2) suggest that Felis domesticus allergen I (Feld I) could be an autoallergen responsible for chronic inflammatory reactions in cats with EGC.] Cat skin may respond with eosinophils to as diverse a group of diseases as allergies, pemphigus, neoplasia, or pyoderma. Thus, specific histological as well as clinical guidelines must be used to make the diagnosis of EGC.
The Lip Ulcer (eosinophilic ulcer, indolent ulcer, rodent ulcer) is usually found on the upper lip of cats. Diagnosis is based on clinical appearance as well as histopathology, which generally reveals hyperplastic ulcerative superficial perivascular dermatitis with eosinophils or neutrophils, mononuclear cells and fibrosis. Blood eosinophilia and tissue eosinophilia are less common than the other diseases in this complex. The major underlying diseases identified with the indolent lip ulcer are flea allergy (3), food allergy and atopic dermatitis; when these are controlled, the lip lesion resolves.
The Eosinophilic Plaque is usually seen on the ventral abdomen or inner thigh. Typical lesions show raised erythematous orange to yellow plaques. Differential diagnosis must include both granulomatous diseases and neoplasia. Biopsy reveals hyperplastic, superficial and deep perivascular dermatitis with eosinophilia and at times a diffuse, eosinophilic dermatitis. Eosinophilic microvesicles and microabscesses may be seen in the epidermis. The eosinophilic plaque has been associated with the underlying diseases of food allergy, flea allergy and atopy.
Feline Eosinophilic Granuloma occurs most commonly in the oral cavity or in a linear fashion on the back legs. A subset of this disease has been associated with mosquito bites (4) and presents as nodules, with or without ulceration, on the face, ears and feet. This condition has also been seen on/within the chin of cats (feline chin edema) and affecting the foot pads. Typically, the lesions have a papular to nodular configuration and histologically show granulomatous dermatitis with multifocal areas of collagen coated with the released substances from degranulated eosinophils (formerly known as 'collagen degeneration'). Eosinophils are common in the biopsies from the face or oral cavity, and there may be a peripheral eosinophilia as well. Eosinophilic granuloma of the hind legs has been associated with the underlying disease of flea allergy; it has also been seen with an apparently genetic predilection in a colony of SPF (specific pathogen-free) cats. The author has seen one case affecting the foot pads, which was associated with certain types of cat litter.
Definitive diagnosis of the eosinophilic granuloma complex MUST be made on histopathology. There are simply too many differential diagnoses which may fool the clinician to make the diagnosis only on visual examination.
Traditionally, these diseases have been treated with intramuscular injections of methylprednisolone acetate (Depomedrol®:UpjohnPharmacia) at 4 mg/kg, given once every two weeks for three injections. The author uses this treatment only IF: the disease has been confirmed by biopsy, there is no evidence of, or no ability to investigate, an underlying cause, and this protocol is only used twice a year at most.
More frequent use of this protocol will lead to the development of diabetes in a very high percentage of cats. If further corticosteroid treatment is needed, oral prednisolone, initially at a dosage of 1 mg/kg q12 h may be used, then tapered to the lowest effective dosage.
In an attempt to avoid corticosteroids, the following treatments have been reported/utilized:
In one study, 4 of 4 eosinophilic granulomas, but 0 of 2 eosinophilic plaques were shown to respond to administration of essential fatty acids (DermCaps®:DVM Pharmaceuticals). Dosages approximated the manufacturer's guidelines. These are well-tolerated medications.
Cyclosporine: a good response to a dose of 25 mg/cat was seen in 6 cases of eosinophilic plaque and 3 cases of oral eosinophilic granuloma in one report. In three cases of indolent lip ulcers, the response was less impressive.
Griseofulvin is well known as a treatment for dermatophytes, but has occasionally been used for its anti-inflammatory effects in skin diseases in people and in cats. Its dosage for the feline eosinophilic granuloma complex is similar to its use in treating dermatophytes: 25 mg/kg twice daily with food. This dosage should be given for at least one month to judge efficacy.
Chlorambucil (Leukeran®: Burroughs Wellcome) is an alkylating agent that alters DNA synthesis. Its mechanism of action in the treatment of the eosinophilic granuloma complex is not understood. It is given at a dosage of 0.1-0.2 mg/kg/day, often in conjunction corticosteroids. The drug is available as a 2 mg tablet, thus, most cats receive 1/2 tablet per day. Daily treatment is continued for four weeks, then changed to alternate day; the lowest possible dosage should be used. Toxicity is uncommon but reversible bone marrow suppression has been noted, and cats on chlorambucil should be monitored with CBCs and platelet counts every 2 to 4 weeks. Vomiting, diarrhea and anorexia have also been reported, but tend to resolve when the medication is given on alternate days.
CANINE EOSINOPHILIC GRANULOMA COMPLEX
Canine eosinophilic granuloma is most commonly reported in Arctic Circle breeds, and is most often seen on the inner thighs or in the mouth. Erythematous to yellow raised nodules with papillated surfaces are typical. Pruritus is variable. Diagnosis is by histology which shows eosinophils and granulomatous inflammation around eosinophilic debriscoated collagen. Treatment is with prednisone at 1 mg/kg q12h for one week, then tapering down over the course of four to six weeks. Occasionally, higher initial dosages are necessary.
Canine eosinophilic furunculosis is probably a related disease. It has been reported in many breeds, but typically is seen in long-nosed large breeds or curious small breeds (i.e., terriers) with potential access to wasps, bees, ants, spiders, etc (5). It is thus felt to be due to arthropod bites or stings. Consistent with this, the disease may be very rapid in onset, leading to nasal/muzzle swelling, exudation and pain. Large, swollen, erythematous lesions on the muzzle are the most common lesions, but in some dogs similar lesions may be seen on the head, periocularly and around the pinna. Impression smears will often show eosinophils. While diagnosis is usually done on a clinical basis, histologic confirmation will show lesions similar to that of the canine eosinophilic granuloma, but with more eosinophilic infiltration into the epidermis and follicular wall, a furunculosis, and fewer areas of eosinophilic debris-coated collagen. Treatment is as reported for the canine eosinophilic granuloma.
1. Fondati A, Fondevila D, Ferrer L. Histopathological study of feline eosinophilic dermatoses. Vet Dermatol 2001;12:333-8.
2. Wisselink MA, van RR, Willemse T. Evaluation of Felis domesticus allergen I as a possible autoallergen in cats with eosinophilic granuloma complex. Am J Vet Res 2002; 63:338-41.
3. Colombini S, Hodgin EC, Foil CS, et al. Induction of feline flea allergy dermatitis and the incidence and histopathological characteristics of concurrent indolent lip ulcers. Vet Dermatol 2001; 12:155-61.
4. Mason KV, Evans AG. Mosquito bite-caused eosinophilic dermatitis in cats. J Am Vet Med Assoc 1991;198:2086-8
5. White SD, Bourdeau P. Hypersensibilité aux dipteres chez les carnivores. Point Vet 27: 203-6, 1995.