Eosinophilic granuloma complex in cats and dogs (Proceedings)

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 article2 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 under­lying diseases identified with the indolent lip ulcer are flea allergy3, food allergy and atopic dermatitis; when these are controlled, the lip lesion resolves. Occasionally infection with Microsporum canis may be responsible for lip ulcers.4

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 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 bites5 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; ‘pouty' cat) 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 cases affec­ting the foot pads 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 tumor, etc), proliferative, non-neoplastic conditions (plasma cell pododermatitis) and infections (herpes virus).

Herpes virus dermatitis is probably under-reported. Persistent ulcerative to necrotizing lesions develop on the face, most typically the nose6 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.

Treatment

• Subcutaneous alpha interferon (Intron A®:Schering; 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 meters, and thus would receive a dose of 290,000-580,000 units) given sub­cutaneously three times weekly for at least six weeks. Side effects are uncommon but malaise may be seen. May be difficult to obtain.

• Concurrent lysine therapy could be considered: a colleague's suggested dose is 250 mg BID for 30 days, then SID to maintain. Use non-propylene glycol containing tablets.

• Recent anecdotal reports are promising for using topical 5% imiquimod cream (Aldara®, 3M Pharmaceuticals), a ‘local immunological response modifier', in the treatment of feline cutaneous herpes infection. Cats generally only tolerate 2-3 treatments per week, due to irritation reactions. The drug comes as a dozen 0.25 gm packets. One packet may supply enough cream for two applications. Cost is around $120 per dozen. There is an anecdotal report of 2 cats developing reversible leucopenia following ingesting (via grooming) imiquimod cream which was placed on their lesions.

• Famcyclovir 40mg/kg tid thus a 5kg cat = ½ of a 500mg tablet tid. Effective – now available as a generic..

Plasmacytic pododermatitis is a rare idiopathic cause of foot pad swelling and ulceration in cats. The initial condition is a soft, nonpainful swelling of the foot pads, 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.7 This disease may be associated with 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 q 12 h9, 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. Researchers using both immunohistology and PCR were unable to identify any organisms in the lesions.

Treatment of feline EGC

Traditionally, these diseases have been treated with intra-muscular 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 (especially feline herpes virus 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®: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 report2 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.

If dermatophytes are present, fluconazole or itraconazole (10 mg/kg q24 h) should be used – previous anecdotal reports of lip ulcers' responses to griseofulvin may in fact have been due to an underlying M. canis infection.

Clavamox has been reported as effective in the treatment of eosinophilic plaques.

Canine eosinophilic granuloma complex

Canine eosinophilic granuloma is most commonly reported in Arctic Circle breeds and Cavalier King Charles Spaniels, 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 is identical to the feline eosinophilic granuloma, with eosinophils and granulomatous inflammation around eosinophilic debris-coated 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 a closely-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. 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.

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