The eosinophilic granuloma complex (EGC) in the cat actually consists of three similar diseases. Despite the name, the three diseases do not always cause granulomas. The presence of eosinophilic degranulation products have been documented coating but not altering the collagen in all of these diseases.

These diseases are best thought of as inflammatory reactions of the skin, often associated with hypersensitivity diseases. Thus, the veterinarian should attempt to search for any underlying diseases. (One article suggest that even 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 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 under lying diseases identified with the indolent lip ulcer are flea allergy, food allergy and atopic dermatitis; when these are controlled, the lip lesion resolves. Occasionally infection with Microsporum canis may be responsible for lip ulcers.

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 hyper plastic, 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 under lying diseases of food allergy, flea allergy and atopic dermatitis.

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 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 oedema, 'pouty' cat) and affecting the footpads. 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 hindlegs has been associated with the underlying disease of flea allergy; it has also been seen with an apparently genetic predilection in a colony of specific pathogen-free (SPF) cats. The author has seen cases affecting the footpads which were 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. These would include neoplasias (lymphoma, mast cell tumour, etc.), proliferative, non-neoplastic conditions (plasma cell pododermatitis) and infections (herpesvirus).

Herpesvirus dermatitis is probably under-reported. Persistent ulcerative to necrotising lesions develop on the face, most typically the nose. Affected cats often have a history of stress, glucocorticoid administration, or chronic ocular or respiratory disease suggesting this skin disease is associated with reactivation of latent herpes virus infection. However, the respiratory signs may be subtle, and owners should be questioned carefully to determine this facet of the history.

Histopathology shows a marked vesicular and ulcerative eosinophilic infiltrate with intranuclear viral inclusion bodies in the epithelium. Unfortunately, the viral inclusions are not always readily seen, and the histology can bear some resemblance to idiopathic or mosquito bite-induced eosinophilic granulomas. Subsequent electron microscopy and polymerase chain reaction evaluation may confirm the virus to be feline herpes 1.

Subcutaneous alpha-interferon (Intron A®: 1 vial contains 3 million units) has appeared beneficial in some cases, sometimes dramatically so. Dosage is approximately 1.5-2 million units/m² (a 5 kg cat has a m² body area of 0.29 m², and thus would receive a dose of 290,000-580,000 units) given subcutaneously three times weekly for at least 6 weeks. Side effects are uncommon but malaise may be seen. Concurrent lysine therapy could be considered: a colleague's suggested dose is 250 mg q12h for 30 days, then q24h to maintain. Use non-propylene glycol containing tablets. Recent anecdotal reports are promising for using topical 5% imiquimod cream (Aldara®), a 'local immunological response modifier', in the treatment of feline cutaneous herpes infection. Cats generally only tolerate two to three treatments per week, due to irritation reactions. The drug comes as a dozen 0.25 g packets. One packet may supply enough cream for two applications. Cost is around US$120 per dozen. There is an anecdotal report of two cats developing reversible leucopenia following ingesting (via grooming) imiquimod cream which was placed on their lesions.

Plasmacytic pododermatitis is a rare idiopathic cause of footpad swelling and ulceration in cats. The initial condition is a soft, non-painful swelling of the footpads, which may progress to ulceration and granulation tissue. Ulceration may lead to pain and lameness. Usually the metacarpal or metatarsal pads are involved but the digital pads may also be affected. Diagnosis is by biopsy, which reveals a diffuse dermatitis with a massive plasma cell infiltration. This disease may be associated with feline immunodeficiency virus (FIV) infection. The best mode of therapy is still undetermined. Corticosteroids have not always been beneficial. Some cases will regress spontaneously. Doxycycline, 5 mg/kg q12h, gold therapy in a regimen as for plasmacytic-lymphocytic stomatitis or surgical removal of affected tissues, are treatments that have been reported as effective. Reports from Europe indicate a high percentage (50%) of these cats are FIV-positive.

Treatment of Feline Eosinophilic Granuloma Complex

Traditionally, these diseases have been treated with intramuscular injections of methylprednisolone acetate at 4 mg/kg, given once every 2 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 (especially feline herpesvirus dermatitis); 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®). Dosages approximated the manufacturer's guidelines. These are well tolerated medications.

 Ciclosporin: a good response to a dose of 25 mg/cat was seen in six cases of eosinophilic plaque and three cases of oral eosinophilic granuloma in one report. In three cases of indolent lip ulcers, the response was less impressive. Another more recent study confirmed these results with a higher dosage range of 10-12.5 mg/kg.

 Chlorambucil 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 with corticosteroids. The drug is available as a 2 mg tablet, thus, most cats receive half a 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 complete blood counts (CBCs) and platelet counts every 2-4 weeks. Vomiting, diarrheoa and anorexia have also been reported, but tend to resolve when the medication is given on alternate days.

 If dermatophytes are present, fluconazole or itraconazole (10 mg/kg q24h) should be used--previous anecdotal reports of lip ulcers' responses to griseofulvin may in fact have been due to an underlying M. canis infection.

 Finally, the author is aware of rare eosinophilic lip ulcers and plaques that respond to staphylocidal antibiotics.

References

1.  Colombini S, Hodgin EC, et al. Induction of feline flea allergy dermatitis and the incidence and histopathological characteristics of concurrent indolent lip ulcers. Veterinary Dermatology 2001; 12: 155-161.

2.  Mason KV, Evans AG. Mosquito bite-caused eosinophilic dermatitis in cats. Journal of the American Veterinary Medical Association 1991; 198: 2086-2088.

3.  Hargis AM, Ginn PE. Feline herpesvirus 1-associated facial and nasal dermatitis and stomatitis in domestic cats. Veterinary Clinics of North America: Small Animal Practice 1999; 29:1281-1290.

4.  Bettenay SV, Mueller RS, et al. Prospective study of the treatment of feline plasmacytic pododermatitis with doxycycline. Veterinary Record 2003; 152: 564-566.

5.  Vercelli A, Raviri G, et al. The use of oral cyclosporin to treat feline dermatoses: a retrospective analysis of 23 cases. Veterinary Dermatology 2006; 17: 201-206.