Feline Eosinophilic Granuloma Complex: An Overview

Tricia A. Starnes, DVM; Kenneth S. Latimer, DVM, PhD; Pauline M. Rakich, DVM, PhD; Perry J. Bain, DVM, PhD

Class of 2003 (Starnes), Department of Pathology (Latimer, Bain), and Athens Veterinary Diagnostic Laboratory (Rakich), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

Introduction

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. EGC is not a specific disease but simply several cutaneous reaction patterns in cats.^5-7 Classically, three lesions have been characterized in feline EGC: (1) the indolent ulcer, (2) the eosinophilic plaque, and (3) the eosinophilic granuloma.^1,3,6 These lesions are grouped together because they may occur in the same patient and may respond to the same therapy.^2,3,5,7

There are no breed predilections to EGC, but females may be predisposed to development of lesions.^3,5-7 Young to middle-age cats usually are affected (average age 3.5 years)^3,4,7 and peripheral lymphadenopathy is often associated with these dermatoses.^4,6,7 Long-standing and more extensive EGC is associated with chronic immune stimulation and an ensuing polyclonal gammopathy.³

The cause of EGC is unknown; however, an underlying hypersensitivity such as a food allergy, atopy, or insect allergy (particularly to fleas and mosquitoes) often has been associated with these lesions.^4,6,7 Since antibiotic therapy clears or significantly improves some lesions, bacterial infection also may be implicated.⁶ However, the response to antibiotics may be due to the immune-modulating effects of the antibiotic therapy rather than any antibacterial properties.⁷ 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.^2,6 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.² 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.²

The main pathogenic events in these lesions are most likely caused by eosinophil recruitment and degranulation.¹ Circulating eosinophils move into tissues (especially into subepithelial sites) in reaction to inflammation prompted by antigen-antibody complexes, parasites, or microorganisms (Fig. 1).⁷ 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.²

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.⁷ Diagnostic tests may be comprised of intradermal skin testing, a hypoallergenic food trial, a flea control trial, and avoidance of mosquitoes.^5,7 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.^4,6 In addition, the clinical appearance of several tumors (squamous cell carcinoma, mast cell tumor, lymphoma, fibrosarcoma, and mammary carcinoma) may be similar to granulomas.^6,7 Cytology and / or biopsy specimens are recommended to exclude neoplasia when any cutaneous mass is evaluated.

Figure 1. Eosinophil from blood of a cat. Notice the characteristic rod- or brick-shaped granules (Wright-Leishman stain).

Dermatohistopathology

The clinical features of EGC cannot be predicted consistently by the histopathological findings of the disease complex and vice versa.^1,7 The three clinical varieties of EGC have common histopathological features; however, unique clinical and histopathological characteristics of the three elements of EGC also have been described.^1,7 A retrospective study was performed on skin samples from 24 cats with EGC. Flame figures and/or large foci of collagen degeneration were seen in every sample.¹ Flame figures are small foci of collagen degeneration in which degenerated collagen fibers are surrounded by degranulated eosinophils.¹ It has been suggested that the use of the terms eosinophilic plaque, indolent ulcer, and eosinophilic granuloma be restricted to clinical dermatology, while the term eosinophilic dermatoses should be used in diagnostic dermatopatholgy.¹

Feline Indolent Ulcer
(Eosinophilic Ulcer, Rodent Ulcer)

Clinical Presentation

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 (Fig. 2).^4-7 Typically, the lesions are well-circumscribed with a raised margin and appear red-brown, alopecic, and glistening.^6,7 These ulcers are painless, non-pruritic, and do not bleed.^1,4-7 Lip ulcers rarely may undergo malignant transformation into squamous cell carcinoma.^5-7

Figure 2. Feline indolent ulcer of the upper lip (© Bristol Biomedical Image Archive, University of Bristol).

Diagnosis

Biopsy is nondiagnostic and reveals a hyperplastic, ulcerated, superficial perivascular to interstitial dermatitis (typically with a preponderance of neutrophils and mononuclear cells) and fibrosis.^1,4,6 Biopsy is primarily used to exclude malignancy.⁵ Eosinophilia rarely is observed in the blood.^4,6

Feline Eosinophilic Plaque

Clinical Presentation

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 (Fig. 3).^4,6,7 The plaques may be single or multiple and measure 0.5 to 7.0 cm in diameter.⁶ They are well circumscribed, raised, round to oval, erythematous, moist, and often ulcerated.^5-7 Pruritus usually is severe.^4-7 The moist character of the lesions is due to ulceration.⁷

Figure 3. Eosinophilic plaques of the medial thighs and groin. Lesions are raised, circumscribed to coalescing, erythematous, and moist.

Diagnosis

Eosinophils are observed commonly on cytologic imprints, but neutrophils and bacteria may prevail if the lesion is secondarily infected.⁴ Biopsy findings are variable and may range from a hyperplastic, superficial and deep, perivascular dermatitis with eosinophilia to interstitial or diffuse eosinophilic dermatitis.^1,4,6 Flame figures may be observed.^1,6 Diffuse spongiosis may be present in the epidermis.⁶ Eosinophilia is common in peripheral blood.^4-6

Feline Eosinophilic Granuloma
(Linear Granuloma, Collagenolytic Granuloma)

Clinical Presentation

Eosinophilic granulomas occur on the caudal thighs, face, and oral cavity (particularly the tongue and palate, Figs. 4 and 5).^4,6,7 Lesions also have been reported on the footpad.^1,7 Cutaneous lesions are typically well-circumscribed, raised, firm, alopecic, erythematous plaques with a characteristic linear configuration.^5-7 These lesions generally are non-painful and non-pruritic.^4-7 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 edema).⁶ If the surface is eroded or ulcerated, a distinctive speckling with pinpoint white foci may be evident.⁶ Cats with oral lesions may be dysphagic.^4,5,7

Figure 4. Eosinophilic granuloma of the digit (© Bristol Biomedical Image Archive, University of Bristol).	Figure 5. Oral eosinophilic granuloma (© Bristol Biomedical Image Archive, University of Bristol).

Diagnosis

Eosinophils are seen commonly in cytologic imprints, but neutrophils and bacteria may prevail if the granuloma is secondarily infected.⁴ Nodular to diffuse granulomatous dermatitis with multifocal areas of flame figure formation are visible in biopsy specimens.⁶ Eosinophils, histiocytes, and multinucleated giant cells^4,6,7 with foci of collagen degeneration⁴ are typical (Fig. 6). Mast cell hyperplasia may be observed occasionally, especially with the application of metachromatic stains (e.g., Giemsa or toluidine blue stains, Fig. 7) Dermal foci of amorphous to granular, eosinophilic to partly basophilic debris are described as being characteristic histopathological traits of eosinophilic granulomas.¹ In chronic lesions, eosinophils are not as prevalent.⁶ Eosinophilia may occur in the blood (especially with oral lesions).^6,7

Figure 6. Histologic section of a cutaneous eosinophilic granuloma with eosinophils, macrophages, and flame figures (hematoxylin & eosin stain).	Figure 7. Histologic section of a cutaneous eosinophilic granuloma with mast cell hyperplasia. Mast cells contain many purple cytoplasmic granules (Giemsa stain).

Treatment of EGC Dermatoses

Identification and treatment of any suspected underlying disease should be performed when managing the various forms of feline EGC.^4,5 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.⁷ Prednisone or prednisolone may be given orally (4.4 mg/kg every 24 hours) until the lesions are healed.^5-7 Alternatively, injections of methylprednisolone acetate (20 mg/cat subcutaneously every 2 -3 weeks until lesions resolve), ^4,6,7 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.⁶ 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).⁶ 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.^4,6 Omega-3/omega-6 fatty acid containing products have been shown to be useful in some cats and reduce glucocorticoid requirements in others.⁶

For lesions that are not responsive to steroid therapy, immunomodulation may be considered as an alternative therapy.^3,5,7 Some cats respond to systemic antibiotics given for 2-3 weeks.^4-7 Other immunomodulating drugs include chlorambucil,⁴ levamisole, thiabendazole, and alpha-interferon.⁶ However, some studies indicate that alpha-interferon is not as useful in treatment of eosinophilic plaques and granulomas.⁶ Other modes of treatment that occasionally are effective include radiotherapy, cryosurgery, laser therapy, surgical excision, and mixed bacterial vaccines.^3,5-7 In addition, unpublished reports demonstrate that occlusive biosynthetic absorbent wound dressing applied to lesions for 48 hours may be beneficial.^6,7 The lesions exhibit a discernible decrease in pruritus following application.⁷ Progestational compounds, such as megestrol acetate, also have been used successfully; however, these drugs are not recommended due to their adverse side effects.^6,7

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.^4,6 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.⁴

References

1. Fondati A, Fondevila D, Ferrer L: Histopathological study of feline eosinophilic dermatoses. Vet Dermatol 6:333-338, 2001.

2. Gelberg HB, Lewis RM, Felsburg PJ, Smith CA: Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex. Am J Vet Res 46:263-265, 1985.

3. MacEwen EG, Hess PW: Evaluation of effect of immunomuodulation on the feline eosinophilic granuloma complex. J Am Anim Hosp Assoc 23:519-525,1987.

4. Medleau L, Hnilica K. Small Animal Dermatology: A Color Atlas and Therapeutic Guide. WB Saunders, Philadelphia, 2001, pp. 254-258.

5. Merchant SR: Diagnosis of feline skin disease based on cutaneous reaction patterns. Compend Contin Educ Pract Vet 16:163,165-166, 1994.

6. Scott DW, Miller WH, Griffin CE: Small Animal Dermatology. WB Saunders, Philadelphia, 2001, pp. 1148-1153.

7. Song MD: Diagnosing and treating feline eosinophilic granuloma complex. Vet Med 89:1141-1145, 1994.

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