Feline indolent ulcers and their significance

Feline indolent ulcers, also referred to as rodent ulcers or eosinophilic ulcers, are a cutaneous reaction pattern in cats that affect the muco-cutaneous junction of the oral cavity. Most indolent ulcers occur on the upper lip near the philtrum or adjacent to the upper canine teeth. These lesions may be presented with bilateral symmetry, or may be asymmetrical, or unilateral. Pruritus and pain are rare. Submandibular lymph node enlargement may be present. Age of onset is variable.

Clinically, lesions associated with eosinophilic lip ulcers exhibit superficial crusting, erythema, and depressed ulcers at the lip margin (Figure 1). These lesions may progress slowly or quite rapidly and are often noted incidentally by the pet owner as the affected cat does not usually exhibit discomfort. Affected cats may be presented for routine evaluation, or for other dermatological concerns, when the indolent ulcer is first noticed. With increasing severity, these lesions enlarge and the ulcer progresses. Despite progression, the lesions typically remain well circumscribed, alongside a concave ulcerated center of granulation tissue that may include areas of yellow to white necrotic tissue. Due to the presence of raised borders around the ulcer and severe localized inflammation, these lesions may appear as firm, proliferative ulcerated masses. In some cases, purulent exudate may be expressed from these lesions (1).

Figure 1.

Indolent ulcer with bacterial infection before treatment.

Although indolent ulcers are quite characteristic visually, identification of such a lesion does not implicate an etiology. As with most cutaneous lesions, recognition of these lesions should trigger not only a treatment plan for the lip lesions, but also diagnostic workup for primary underlying causes that can be responsible for development of indolent ulcers. These underlying possibilities most commonly include allergic disease, including flea bite hypersensitivity, feline atopy (non-flea, nonfood allergic dermatitis), insect bite hypersensitivity, and food allergy. When allergic disease is suspected as the underlying cause, secondary bacterial infection of the lesion should also be considered. Bacterial involvement is more often a factor than previously thought (2,3).

One major differential diagnosis for the feline indolent ulcer lesion is squamous cell carcinoma. Additional differential diagnoses include fungal infection, feline herpes virus type 1 infection, trauma, lymphoma, and mast cell tumor (1,4). Histopathology helps to differentiate indolent ulcer from other disease. Histopathology of the indolent ulcer lesion demonstrates epidermal hyperplasia and eosinophilic infiltration of the dermis. Other inflammatory cells may also be present. Mucin deposition in the epidermis can sometimes be seen (1).

Diagnostic workup

In many cases, a preliminary diagnosis is made based on appearance of the lesion. Despite characteristic lesions indicating underlying allergy to be the most likely cause, especially in younger cats, other possibilities should always be considered for the diagnostic workup. Diagnostic tests selected can vary from patient to patient based on presenting factors. A simple and effective diagnostic test that can help with initial assessment of these lesions is impression cytology from the lesion. Impression cytology should help assess for presence of bacterial infection within the lesion. Cytology of these lesions typically demonstrates eosinophilic inflammation, and bacteria with or without neutrophilic inflammation. When infection is noted, appropriate antibiotic therapy is indicated while initiating diagnostic workup for underlying allergy. Indolent ulcers should be suspected as lesions of deep pyoderma, thus potential for 4 to 6 weeks of antibiotic therapy should also be considered. Multiple reports of empirical antibiotic use as an effective treatment option for some patients are part of the veterinary literature (1,2). Due to recent concerns surrounding empirical antibiotic use with regard to development of antimicrobial resistance in veterinary and human health, such antibiotic use is best avoided. Moreover, the suggested antibiotic dosing and length of therapy specific to treatment of feline indolent ulcer is quite generalized in the published literature (1,2). A combination of impression cytology, clinical impression of the lesion, and bacterial culture and sensitivity testing is a much more reliable method of determining use of and length of antibiotic therapy needed for an individual patient.

As part of initial allergy workup, flea control for all household pets as well as a dietary elimination trial can be initiated, using either a novel single protein diet or a hydrolyzed protein diet.

Punch biopsy for histopathology is the confirmatory test, while ruling out other differential diagnoses such as neoplasia. This is best pursued when superficial infection within the lesions has been ruled out by impression cytology. At the time of collection of a biopsy sample for histopathology, a sample for bacterial culture should be taken to rule out deep pyoderma that was not evident on superficial cytology testing. If deep pyoderma is in fact noted, culture-based antibiotic therapy should help resolve such an infection.

Additionally, thorough dermatological and oral evaluation is a must for all cats presented with rodent ulcers. As a large proportion of affected cats have underlying allergies, other clinical signs suggestive of allergy may be present. Indolent ulcers form a part of the feline Eosinophilic Granuloma Complex (EGC). Other manifestations of EGC include eosinophilic plaques and eosinophilic granulomas affecting the skin or within the oral cavity. These may be noted in conjugation to the indolent ulcer lesions. Additional signs of feline allergic disease such as self-inflicted alopecia (bilaterally symmetrical alopecia of the ventral trunk), miliary dermatitis, generalized pruritus (including over-grooming or head and neck pruritus) may also be present. Lack of these additional signs does not eliminate the possibility of an underlying allergic process, but presence of additional signs is considered very helpful in setting up a diagnostic and treatment plan for the patient.

Treatment of indolent ulcers

Various treatments have been described in the literature including antibiotic, anti-inflammatory, and immunosuppressive therapies (Figure 2) (1,2,5). As with most secondary implications of allergic disease, these lesions are more amenable to therapy when the primary process that drives lesion formation is addressed and controlled. As indolent ulcers have been documented to develop from flea bite hypersensitivity (6), flea control is a simple, effective treatment option for the flea allergic patient. All household pets should be treated for fleas, irrespective of the clinician’s ability to prove presence of a flea infestation. Dietary elimination trials followed by controlled provocation challenge should help diagnose or rule out the presence of food allergy. Provocation challenges are preferably pursued after resolution of the lesion and infection, and are more straightforward to evaluate when a previously pruritic patient is not demonstrating pruritic behavior anymore. If indolent ulcers (and additional allergic signs) persist or recur despite appropriate workup, this suggests possible presence of environmental allergy (feline atopy). In atopic cats, intra-dermal allergy testing or serum allergy IgE testing should be conducted to identify offending allergens so that allergen specific desensitization therapy may be pursued.

Figure 2.

Indolent ulcer resolving after 4 weeks on dietary elimination trial and culture-based antibiotic therapy.

Symptomatic anti-inflammatory therapy can be used to help resolve lesions while the underlying disease is investigated. It is important to remember that despite its visually striking appearance and severe ulceration, most cats that exhibit the lesion are visibly comfortable and are active cats with a good appetite. The term “indolent ulcer” originates from the Latin term indolens, which means “without pain.” Thus, need for strong anti-inflammatory therapy should not be assumed as the condition lends itself to appropriate diagnostic workup and follow-up evaluations. It is also worth reiterating that appropriate use of antibiotic therapy alone may help improve lesions even without administration of glucocorticoids or cyclosporine, while allergy workup is pursued (3).

If the patient exhibits discomfort or additional clinical symptoms, corticosteroid therapy or cyclosporine therapy can be administered to help resolve inflammation associated with the lesion. Lesions tend to recur when symptomatic therapy is tapered or discontinued if the underlying disease has not been addressed or if secondary infection has not resolved. Long-term immuno-suppressive drug therapy is best avoided and replaced with thorough workup of underlying primary disease. Long-acting injectable corticosteroids such as methyl-prednisolone acetate should be avoided as the risk of side effects is typically more severe than the condition itself (i.e., development of diabetes mellitus, urinary infection, cardiac effects, fragile skin) (7,8).

Other methods of treatment reported to be occasionally successful include radiotherapy, cryosurgery, laser therapy, surgical excision, mixed bacterial vaccines, gold salt aurothioglucose, immunomodulating drugs such as oral or sub-cutaneous low dose interferon alfa, and oral essential fatty acid supplementation (1,8).

Prognosis

If the underlying disease is identified and managed successfully, prognosis for rodent ulcer resolution is excellent. If the underlying disease is not controlled, recurrence of the lesion is likely. Cats with recurring lesions for which no underlying cause can be found usually require long-term drug therapy to keep lesions in remission. These cats have a poorer prognosis as they may become refractory to or may develop unacceptable adverse effects as the result of medical therapy.