Feline eosinophilic granuloma complex (EGC) is a common inflammatory skin disease of cats, which consists of a group of lesions that affect the skin, mucocutaneous junctions, and oral cavity. Feline eosinophilic dermatoses is the term now used to encompass EGC lesions[1].

• EGC is not a specific disease but simply several cutaneous reaction patterns in cats. Classically, three lesions have been characterized in feline EGC, although they are essentially different reaction patterns reflecting a hypersensitivity-reaction to identifiable causes (e.g. atopy, food allergy dermatitis and flea allergy dermatitis)[2]:
• indolent ulcer (rodent ulcer)
• eosinophilic plaque
• eosinophilic granuloma.

These lesions are grouped together because they may occur in the same patient and may respond to the same therapy. There are no breed predilections to EGC, but females may be predisposed to development of lesions. Young to middle-age cats usually are affected (average age 3.5 years) and peripheral lymphadenopathy (swollen glands) is often associated with these dermatoses. Long-standing and more extensive EGC is associated with chronic immune stimulation and an ensuing polyclonal gammopathy.

Causes

The cause of EGC is unknown; however, a propensity of eosinophils suggests that viral infections such as FHV[3] and underlying hypersensitivities such as a food allergy dermatitis, atopy, flea allergy dermatitis or mosquito-bite hypersensitivity have been associated with these lesions. Since antibiotic therapy clears or significantly improves some lesions, bacterial infection also may be implicated. However, the response to antibiotics may be due to the immune-modulating effects of the antibiotic therapy rather than any antibacterial properties. A genetic predisposition to EGC may exist because eosinophilic granulomas and indolent ulcers have been observed in a colony of specific pathogen-free cats and other cats with limited genetic diversity[4]. Also, it has been postulated that EGC may be an autoimmune phenomenon because the presence of circulating antiepithelial autoantibodies has been demonstrated in one study of affected cats. Conversely, due to the severe epidermal injury and dermal reaction in cats with EGC, altered antigens may have been released resulting in production of autoantibody.

Pathology

The main pathogenic events in these lesions are most likely caused by eosinophil recruitment and degranulation. Circulating eosinophils move into tissues (especially into subepithelial sites) in reaction to inflammation prompted by antigen-antibody complexes, parasites, or micro-organisms. Since eosinophils are attracted to and phagocytize antigen-antibody complexes, the presence of eosinophils in the EGC indicates that it is an immune-mediated disease. Many other diseases may have a similar clinical presentation as EGC. Due to the correlation with hypersensitivity disorders, a diagnostic evaluation for allergic skin disease should be conducted[5].

Feline Indolent Ulcer

(Eosinophilic Ulcer, Rodent Ulcer) – Feline indolent ulcer is a common cutaneous, mucocutaneous, and oral mucosal lesion. Although, most indolent ulcers occur unilaterally on the upper lip, they also may appear bilaterally in the oral cavity or in other cutaneous locations. Typically, the lesions are well-circumscribed with a raised margin and appear red-brown, alopecic, and glistening. These ulcers are painless, non-pruritic, and do not bleed. Lip ulcers rarely may undergo malignant transformation into squamous cell carcinoma. Biopsy is nondiagnostic and reveals a hyperplastic, ulcerated, superficial perivascular to interstitial dermatitis (typically with a preponderance of neutrophils and mononuclear cells) and fibrosis. Biopsy is primarily used to exclude malignancy. Eosinophilia rarely is observed in the blood.

Feline Eosinophilic Plaque

Feline eosinophilic plaque is a common cutaneous lesion which may arise anywhere on the skin, but is most commonly found on the ventral abdomen and medial thighs. The plaques may be single or multiple and measure 0.5 to 7.0 cm in diameter. They are well circumscribed, raised, round to oval, erythematous, moist, and often ulcerated. Pruritus usually is severe. The moist character of the lesions is due to ulceration. Eosinophils are observed commonly on cytologic imprints, but neutrophils and bacteria may prevail if the lesion is secondarily infected. Biopsy findings are variable and may range from a hyperplastic, superficial and deep, perivascular dermatitis with eosinophilia to interstitial or diffuse eosinophilic dermatitis. Flame figures may be observed. Diffuse spongiosis may be present in the epidermis. Eosinophilia is common in peripheral blood[6].

Feline Eosinophilic Granuloma

Also known as linear granuloma or collagenolytic granuloma, eosinophilic granulomas occur on the caudal thighs, face, and oral cavity (particularly the tongue and palate). Lesions also have been reported on the footpad. Cutaneous lesions are typically well-circumscribed, raised, firm, alopecic, erythematous plaques with a characteristic linear configuration. These lesions generally are non-painful and non-pruritic. Lesions on the face and in the oral cavity have a papular to nodular configuration and are a common reason for lower lip swellings (pouting cats) and asymptomatic swollen chins (fat-chinned cats, feline chin oedema). If the surface is eroded or ulcerated, a distinctive speckling with pinpoint white foci may be evident.

Cats with oral lesions may be dysphagic. Eosinophils are seen commonly in cytologic imprints, but neutrophils and bacteria may prevail if the granuloma is secondarily infected. Nodular to diffuse granulomatous dermatitis with multifocal areas of flame figure formation are visible in biopsy specimens. Eosinophils, histiocytes, and multinucleated giant cells with foci of collagen degeneration are typical. Mast cell hyperplasia may be observed occasionally, especially with the application of metachromatic stains. Dermal foci of amorphous to granular, eosinophilic to partly basophilic debris are described as being characteristic histopathological traits of eosinophilic granulomas. In chronic lesions, eosinophils are not as prevalent. Eosinophilia may occur in the blood (especially with oral lesions)[7][8][9].

Diagnosis

Diagnostic tests may be comprised of intradermal skin testing, a hypoallergenic food trial, a flea control trial, and avoidance of mosquitoes. These tests are most commonly performed when EGC is non-responsive to glucocorticoid therapy. Other differential diagnoses to consider are infectious ulcers or granulomas (bacterial, fungal, FeLV-associated) and trauma. In addition, the clinical appearance of several tumours (squamous cell carcinoma, mast cell tumour, lymphoma, fibrosarcoma, and mammary tumours may be similar to granulomas. Cytology and/or biopsy specimens are recommended to exclude neoplasia when any cutaneous mass is evaluated.

Treatment

Identification and treatment of any suspected underlying disease should be performed when managing the various forms of feline EGC. Immunosuppressive therapy is the most common treatment and systemic glucocorticoids are often effective. Cats have fewer steroid receptors on their cells and thus require higher doses of glucocorticoids than most other species. Prednisone or prednisolone may be given orally (4.4 mg/kg every 24 hours) until the lesions are healed. Alternatively, injections of methylprednisolone acetate (20 mg/cat subcutaneously every 2 -3 weeks until lesions resolve), or oral administration of glucocorticoids (dexamethasone at 0.4 mg/kg every 24 hours or triamcinolone at 0.8mg/kg every 24 hours) may be effective[10].

Recurrent lesions may be managed with oral glucocorticoids given every other day or repeated subcutaneous injections of methylprednisolone (which should never be given more frequently than every 2 months). Considerable improvement of the lesions should be evident within 2-4 weeks.4 When the lesions have improved, glucocorticoid therapy should be gradually tapered to the lowest possible dosage. Omega-3/omega-6 fatty acid containing products have been shown to be useful in some cats and reduce glucocorticoid requirements in others. For lesions that are not responsive to steroid therapy, immunomodulation may be considered as an alternative therapy. Some cats respond to systemic antibiotics given for 2-3 weeks.

Other immunomodulating drugs include chlorambucil, levamisole, thiabendazole, and alpha-interferon. However, some studies indicate that alpha-interferon is not as useful in treatment of eosinophilic plaques and granulomas. Other modes of treatment that occasionally are effective include radiotherapy, cryosurgery, laser therapy, surgical excision, and mixed bacterial vaccines. In addition, unpublished reports demonstrate that occlusive biosynthetic absorbent wound dressing applied to lesions for 48 hours may be beneficial. The lesions exhibit a discernible decrease in pruritus following application. Progestational compounds, such as megestrol acetate, also have been used successfully; however, these drugs are not recommended due to their adverse side effects[11].

Two groups of “alternative” therapies, most of which have been tried in small numbers of cases, only in prospective studies or have been empirically / anecdotally reported as effective, are available.

The first group of “alternative” treatments includes lysine, antihistamines and essential fatty acids. These drugs have few reported potential side effects but also few possibilities to work in case of lack of therapeutic efficacy of glucocorticoids.

The second group of “alternative” treatments includes, among others, the following immunomodulatory drugs (CBC, chemistry profile and urinalysis should be periodically checked during therapy)

a) Cyclosporine A. It is given orally (5-10 mg/Kg every 24 hours) for 4 to 8 weeks then tapered to alternate days. Cyclosporine A is a promising drug to treat EGC, due to its demonstrated ability to inhibit airway eosinophilic inflammation in an experimentally induced feline model of atopic asthma.

b) Interferon alpha-2a. It may be administered orally (30-60 units/cat per day) for 30 consecutive days, or on alternate weeks. It has been demonstrated that interferon alpha inhibits the release of granule proteins from human eosinophils[12].

c) Famciclovir – Oral famciclovir was used to treat signs considered referable to FHV-1 in 10 cats: four had primary ocular disease, two had rhinosinusitis and four had FHV-1 associated dermatitis. Patients treated in Australia (five cats) and Europe (one cat) were given 62.5 mg of famciclovir once or twice daily. Four cats treated in the USA were given 125 mg three times daily. Famciclovir was uniformly well tolerated and, in all cases, had a positive impact on the patient’s condition. The apparent improvement in lesions was superior to what had been achieved previously using other therapeutic strategies. One cat with severe destructive rhinosinusitis was significantly improved by a 4-month course of famciclovir in combination with antibacterials. Corneal sequestra detached in two out of three cats treated; cats with ocular signs were qualitatively more comfortable, with reduced clinical signs and an improved appearance of the eyes. Critically, oral famciclovir therapy was considered more convenient than topical ocular therapy. All four cats with FHV-1 associated dermatitis improved substantially, although relapse occurred subsequently in three patients (Malik et al, 2009).

Prognosis

The prognosis of ECG is variable. Young cats often have a better prognosis. In cats less than 1 year of age, eosinophilic granulomas may regress spontaneously over a period of 3 to 5 months. In individuals with recurring lesions without a determined underlying cause, long-term therapy typically is required to keep the lesions in remission. Since these cats may become refractory to or develop side effects from medical therapy a poorer prognosis is given.

References

↑ Bloom, PB (2006) Canine and feline eosinophilic skin diseases. Vet Clin N Am Small Anim Pract 36:141-160
↑ Lee, M, Bosward, KL & Norris, J (2010) Immunohistological evaluation of feline herpesvirus-1 infection in feline eosinophilic dermatoses or stomatitis. JFMS 12:72-90
↑ Malik R, Lessels NS, Webb S, Meek M, Graham PG, Vitale C, Norris JM, Power H. (2009) Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. J Feline Med Surg. 11(1):40-8.
↑ Guaguere, E & Prelaud, P (2000) A practical guide to feline dermatology. Merial, France
↑ Gelberg HB, Lewis RM, Felsburg PJ, Smith CA (1985) Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex. Am J Vet Res 46:263-265
↑ Song MD (1994) Diagnosing and treating feline eosinophilic granuloma complex. Vet Med 89:1141-1145
↑ MacEwen EG, Hess PW (1987). Evaluation of effect of immunomuodulation on the feline eosinophilic granuloma complex. J Am Anim Hosp Assoc 23:519-525
↑ Medleau L & Hnilica K (2001) Small Animal Dermatology: A Color Atlas and Therapeutic Guide. WB Saunders, Philadelphia, pp. 254-258.
↑ Merchant SR (1994) Diagnosis of feline skin disease based on cutaneous reaction patterns. Compend Contin Educ Pract Vet 16:163,165-166
↑ Tricia A. Starnes, DVM; Kenneth S. Latimer, DVM, PhD; Pauline M. Rakich, DVM, PhD; Perry J. Bain, DVM, PhD
↑ Fondati A, Fondevila D, Ferrer L (2001) Histopathological study of feline eosinophilic dermatoses. Vet Dermatol 6:333-338
↑ Scott DW, Miller WH, Griffin CE (2001) Small Animal Dermatology. WB Saunders, Philadelphia, pp. 1148-1153.