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Eosinophilic granuloma complex

ISSN 2398-2950


Introduction

  • A term used to describe three different types of cutaneous reaction patterns with similar etiology, diagnosis and management.
  • Cause: various, most commonly hypersensitivity (particularly flea bite hypersensitivity).
  • Signs: indolent ulcer (ulcerated lesion on the upper lip), eosinophilic plaque (erythematous, raised, exudative lesions anywhere on the skin), collagenolytic granuloma (linear or nodular lesions anywhere on the skin or in the oral cavity).
  • Diagnosis: history, clinical signs, histopathology, trial treatments for the underlying cause.
  • Treatment: identification and correction of underlying cause or long-term symptomatic treatment if unable to identify underlying cause.
  • Prognosis: excellent provided underlying cause identified and treated, guarded otherwise.
    Print off the owner factsheet Feline eosinophilic granuloma complex Feline eosinophilic granuloma complex to give to your client.

Presenting signs

Indolent ulcer

  • Focal area of ulceration with a raised margin   Skin: eosinophilic granuloma - mouth  .
  • Usually upper lip   Skin: eosinophilic ulcer on mouth - DSH  .
  • No pain or pruritus.

Eosinophilic plaque

  • Focal area of intense pruritus.
  • Erythematous, raised, exudative .
  • Anywhere on the skin or mucocutaneous junction but commonly abdomen and medial aspects of hind legs. The oral cavity may be affected.

Collagenolytic granuloma

  • Linear or nodular lesions.
  • Anywhere on the skin or in the oral cavity.
  • No pain or pruritus.

Age predisposition

  • Collagenolytic granuloma: 0.5-5 years old (although small number of cases makes interpretation difficult).

Pathogenesis

Etiology

Hypersensitivity

Ectoparasites

Infection

Other causes

  • Genetic factors.

Pathophysiology

  • Eosinophilic plaques and collagenolytic granuloma: hypersensitivity thought to be causative in most cases.
  • Indolent ulcers Indolent ulcer: cause unclear? hypersensitivity thought to be involved.
  • Why an individual cat with a hypersensitivity develops a particular manifestation of EGC is unknown.
Eosinophilic plaque and collagenolytic granuloma
  • Inflammation (typically hypersensitivity or ectoparasites)   →   cellular infiltration by mast cells and eosinophils.
  • Mast cell degranulation   →   release of eosinophil chemotactic substances.
  • Eosinophilic granules   →   down regulation of inflammation, parasite destruction and collagenolysis.

Indolent ulcer

  • Unknown.

Diagnosis

Presenting problems

  • Ulceration.
  • Pruritus.
  • Nodules.
  • Papules.

Client history

Indolent ulcers
  • Ulceration upper lip with no associated pain or pruritus.

Eosinophilic plaque

  • Pruritus precedes development of the lesion.
  • Single or multiple lesions anywhere on body.
Collagenolytic granuloma
  • Asymptomatic chin swelling
  • Skin lesions with associated pruritus.

Clinical signs

Indolent ulcers
  • Focal area of ulceration with a raised pink to white proliferative margin and brown to yellow depressed center.
  • Unilateral   Eosinophilic granuloma: ulcer on lip  or bilateral on upper lip.
  • Painless.
  • Non-pruritic:
  • Ulcer overlying a thickened nodule.
  • Acute non-ulcerated nodule or swelling.
  • Bilateral.
  • Local peripheral lymphadenopathy may be present.
  • Occasionally occur in the oral cavity and other areas of the skin.

Eosinophilic plaque

  • Focal area of intense pruritus.
  • Erythematous, raised, exudative.
  • The abdomen   Skin: eosinophilic plaque on flank  and medial aspects of the hind legs are typically affected   Eosinophilic granuloma: ulcer on leg  .
  • Single or multiple.
  • Round to oval, 0.5-7cm diameter.
  • Seen anywhere on the skin or mucocutaneous junction or oral cavity.
  • Ulceration and crusting.
  • Cobblestone appearance to plaque.
  • Peripheral lymphadenopathy.

Collagenolytic granuloma

  • Linear or nodular lesion.
  • Raised cord-like bands 2-4 mm wide and 5-10 mm long of pink to yellow firm alopecic areas extending along the posterior aspect of the hind legs   Eosinophilic granuloma: linear form  .
  • No pain or pruritus.
  • Well-circumscribed papular, nodular or plaque lesion.
  • Asymptomatic chin swelling (feline chin edema).
  • Oral lesions: smooth, glistening, nodular and usually non-ulcerated, especially pharynx or tongue   Mouth: eosinophilic granuloma complex  .
  • Anywhere on skin, mucocutaneous junction or oral cavity.
  • Erosion or ulceration of surface.
  • White speckling of eroded/ulcerated surface.
  • Lower limb swelling or nodules.
  • Bridge of the nose, pinnae and footpads (mosquito bite hypersensitivity).
  • Ulceration upper lip.
  • Local peripheral lymphadenopathy may be present.
  • Pruritus.

Diagnostic investigation

Other
  • Flea comb: fleas or flea feces   Flea feces    Flea feces: test  .
Many cats with flea bite hypersensitivity are overgrooming and little or no flea fecal material is found. It can be worthwhile checking other household cats for signs of flea presence.
  • Skin scrapes Scraping: skin for ectoparasites and dermatophyte-infected hairs.

Cytopathology

  • Impression smear, light skin scrape or needle aspiration for nodules.
  • High numbers of eosinophils (eosinophilic plaque and collagenolytic granuloma) +/- bacteria and neutrophils if secondary bacterial infection.

Histopathology

  • Indolent ulcer: chronic ulcerative dermatitis with neutrophils, plasma cells and mononuclear cells.
  • Eosinophilic plaque: spongiotic or hyperplastic epidermatitis +/- microvesicles in epidermis. Dermal infiltrate is diffuse or perivascular and consists primarily of massive numbers of eosinophils with fewer numbers of mast cells. There is no granuloma formation.
  • Nodular to diffuse granulomatous dermatitis with multifocal areas of collagen degeneration. Eosinophils and multinucleated histocytic giant cells are common and flame figures may be seen. Mucinosis of the epidermis and hair follicle outer root sheath, focal eosinophilic folliculitis or furunculosis and focal eosinophilic panniculitis may be present.
  • Rules out certain differentials - especially important for the neoplastic differentials for nodular and ulcerative presentations.
Hematology
  • Eosinophilic plaque and collagenolytic granuloma: eosinophilia.

Bacteriology

  • If rods found on cytology or if antibiotics have been used previously then culture and sensitivites are indicated.

Intradermal skin tests

  • Use to aid treatment of atopic dermatitis Skin: atopic dermatitis and occasionally for insect bite hypersensitivities.

Other

Confirmation of diagnosis

Discriminatory diagnostic features

  • Cytology.
  • Hematology.

Definitive diagnostic features

  • Histopathology.

Differential diagnosis

Treatment

Initial symptomatic treatment

Standard treatment

Ectoparasites

Hypersensitivity

Bacterial skin disease

Hypersensitivity Cases in which no cause can be identified
Oral antibiotics
  • Oral antibiotics for skin Therapeutics: antimicrobial drug 3-6 weeks   →   partial or complete remission of some indolent ulcers and collagenolytic granulomata.

Systemic glucocorticoids

  • Prednisolone Prednisolone if no response to oral antibiotics:
  • Injectable methylprednisolone Methylprednisolone (4-5 mg/kg IM, maximum 20 mg in single dose) q2 weeks until a beneficial response is seen (typically 2-3 treatments). Once in remission q2 months or discontinue if possible.
  • Oral glucocorticoids: may be used as an alternative to methylprednisolone but anecdotal reports suggest that this form of therapy may be less effective. High dose prednisolone Prednisolone  4-5 mg/kg q24h, once in remission 2 mg/kg q48h. Methylprednisolone Methylprednisolone 4 mg/kg/day. Triamcinolone Triamcinolone 0.5-0.75 mg/kg/day. If lesions resolve taper to lowest alternate day dosage (may be possible to taper triamcinolone to twice weekly). Dexamethasone Dexamethasone (solution) 0.05-0.2 mg/kg every 1-3 days can also be used.
For all these corticosteroids it is more effective to use a higher dose initially to obtain control of the lesion and to then reduce the dose only once the lesion has disappeared. Concurrent elimination of exposure to any antigen should also occur.

Immunomodulating drugs

  • If no response to glucocorticoids or if side effects are unacceptable.
  • Ciclosporin (cyclosporine) Ciclosporin 7mg/kg/day orally.
  • Chlorambucil  Chlorambucil  (0.1-0.2 mg/kg q24h reducing to q48h) if beneficial response.
  • Megestrol acetate Megestrol acetate is not recommended due to potential side effects. Use only in cases that do not respond to any other therapy. Dose: 2.5-5 mg/cat q48h tapering to 2.5-5 mg q2-14d.

Surgery

  • Surgical excision of lip ulcers and focal collagenolytic granulomas (may leave deformities).
  • Cryosurgery: poor results.
  • Radiation therapy.

Monitoring

  • History and clinical signs.
  • Long-term glucocortoids Therapeutics: glucocortoids: q 6-12 months: hematology, biochemistry and urinalysis to screen for side-effects.

Prevention

Outcomes

Prognosis

  • Variable depending on whether underlying cause corrected.
  • Long-term symptomatic management usually required in cases where the underlying cause cannot be identified.

Expected response to treatment

  • Improvement in clinical signs after 3-6 weeks.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Wildermuth B E, Griffin C E & Rosenkrantz W S (2012) Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydreate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled propspective study. Veterinary Dermatology 23 (2), 110-8 PubMed.
  • Persico P, Roccabianca P, Corona A et al (2011) Detection of feline herpes virus 1 via PCR and immunohistochemistry in cats with ulcerative facial dermatitis, eosinophilic granuloma complex reaction pattern and mosquito bite hypersensitivity. Veterinary Dermatology 22 (6), 521-527 PubMed.
  • Lee M, Bosward K L, Norris J M (2010) Immunohistolical evaluation of feline herpes-1 infection in feline eosinophilic dermatoses or stomatitis. Journal of Feline Medicine and Surgery 12 (2), 72-79 PubMed.
  • Leistra W H, Van Oost B A & Willemse T (2005) Non-pruritic granuloma in Norwegian Forrest cats. Veterinary Record 156 (18), 575-577 PubMed.
  • Bardagí M, Fondati A, Fondevila D et al (2003) Ultrastructural study of cutaneous lesions in feline eosinophilic granuloma complex. Veterinary Dermatology 14 (6), 297-303 PubMed.
  • Columbini S, Hodgin E C, Foil C S et al (2001) Induction of feline flea allergy dermatitis and the incidence and histopathological characteristics of concurrent indolent lip ulcers. Veterinary Dermatology 12 (3), 155-161 PubMed.
  • Fondati A, Fondevila D & Ferrer L (2001) Histopathological study of feline eosinophilic dermatoses. Veterinary Dermatology 12 (6), 333-338 PubMed.
  • Mason K V & Evans A G (1991) Mosquito bite-caused eosinophilic dermatitis in cats. Journal of the American Veterinary Medical Association 198 (12), 2086-2088 PubMed.
  • Pentlarge V (1991) Eosinophilic conjunctivitis in five cats. Journal of the American Animal Hospital Association 27 (1), 21-28 PubMed.
  • Gelberg H B, Lewis R M, Felsburg P J et al (1985) Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex. Am J Vet Res 46 (1), 263-265 PubMed.
  • Langford L W, Selby L A (1979) Feline eosinophilic granuloma complex - a clinicoepidemiologic study of 32 cases. Vet Med Small Anim Clin 74 (5), 665-667 PubMed.

Other sources of information

  • Miller W H, Griffin C E & Campbell K L (2013) Feline eosinophilic granuloma complex. In: Muller and Kirk’s Small Animal Dermatology. Eds: Miller W H, Griffin C E & Campbell K L. Elsevier Mosby, St Louis Missouri pp 714.
  • Gross T et al (2005) Ulcerative and crusting dermatoses of the epidermis. In: Skin Diseases of the Dog and Cat, Clinical and Histopathologic Diagnosis. Ames Blackwell Science pp 116
  • Gross T et al (2005) Nodular and diffuse diseases of the dermis with prominent eosinophils, neutrophils or plasma cells. In: Skin Diseases of the Dog and Cat, Clinical and Histopathologic Diagnosis. Ames Blackwell Science pp 342.
  • Rosenkrantz W S (1992) Feline eosinophilic granuloma complex. In: Current Veterinary Dermatology the science and art of therapy. Eds: Griffin C E, Kwochka K W, MacDonald J M. Mosby Year Book, St Louis pp 319.
  • Power H (1990) Eosinophilic granuloma in a family of specific pathogen-free cats. In: Proceedings of the Annual Members Meeting of the American Academy of Veterinary Dermatology and American College of Veterinary Dermatology.