Feline herpesvirus 1 (FHV-1) belongs to the subfamily Alphaherpesvirinae, genus Varicellovirus. Like the other α-herpesvirus it shows a predilection for nervous tissue and, after the acute phase of infection, is able to persist in a latent form in the cells of the host’s trigeminal ganglia. This virus can be reactivated after long periods of latency; reactivation occurs in conditions of immunodepresssion which may develop as a result of stress, concomitant diseases, or treatment with glucocorticoids. FHV-1 is the causal agent of feline infective rhinotracheitis and is also responsible for glossitis, keratitis, conjunctivitis, chronic sinusitis, corneal sequestration, eosinophilic keratoconjunctivitis and anterior uveitis. Rarely, it can cause erosive and ulcerative-crusting dermatitis and stomatitis.
CLINICAL SIGNS
The dermatitides induced by FHV-1 are predominantly localised to the face (Fig. 1) and are characterized by erosions, ulcers and crusts associated with variable degrees of erythema, exudation and swelling.
Vesicular lesions have also been reported. The lesions tend to occur in the areas of skin in closest contact with the secretions in which the virus is eliminated, such as the palpebrae, in particular the median canthus, the philtrum, the nostrils and lips, and in areas innervated by the trigeminal nerve, such as the periorbital area, the muzzle and the dorsum of the nose. In some cases the dermatitis can also affect the limbs (Fig. 2), particularly the distal parts of the anterior limbs, the ears and ventral regions. The pathogenesis of these lesions is unclear, but it is thought that they are associated with direct contact of areas of the skin with lachrymal or nasal secretions and/or with the ulcerated areas of skin as the cat cleans itself. In some patients the lesions may be distributed symmetrically and, thereby, mimic an autoimmune disease.
Pruritus is usually either absent or modest and, when present, is often associated with secondary bacterial infections, as is the development of regional lymphadenopathy. There is no predilection for particular breeds, gender or age group. It has been shown that the virus can cause cutaneous lesions in the cat and cheetah without preceding or concomitant respiratory or ophthalmological symptoms. Furthermore, FHV-1 can trigger the development of erythema in multiforme the cat.
DIFFERENTIAL DIAGNOSIS
A viral cause for skin lesions should always be suspected in kittens and unvaccinated cats, including those with respiratory and/or conjunctival signs with or without systemic signs. In the chronic forms, particularly when there is no past history or the dermatological signs are not accompanied by respiratory and/or ophthalmological signs, the differential diagnoses include hypersensitivity to stings or bites by mosquitoes or arthropods, diseases associated with eosinophilic granuloma complex, some neoplastic disorders such as squamous cell carcinoma, pemphigus foliaceus, bacterial infections, other viral dermatitides such as those induced by Calicivirus or poxviruses, and idiopathic ulcerative dermatitis in the Persian cat.
DIAGNOSIS
The diagnosis can be made from histological examination of the skin lesions and/or ancillary investigations, such as polymerase chain reaction (PCR) analysis and immunohistochemistry. In the case of suspected herpetic dermatitis it is always wise to contact the local reference laboratory to organize the procedures for collecting and sending the samples.
Histopathological studies
Specimens of both the ulcerated areas and the erythematous areas should be taken when possible. Peri-ocular and palpebral regions, on the other hand, should not be sampled in order to avoid scarring which could cause functional impairment. The use of small punch biopsies (4 mm) guarantees a better aesthetic outcome when biopsies of facial lesions are necessary.
The histological diagnosis can only be made by the identification of the intranuclear inclusion bodies caused by the virus. Although these can be difficult to detect, they may be recognized in the integral areas adjacent to ulcers or foci of necrosis. They are present in the superficial layers of the epidermis, in the follicular epithelium and, more deeply, in the sebaceous glands. Immunohistochemical studies and PCR can also be carried out on paraffin-fixed samples in order to confirm that any inclusion bodies observed are due to FHV-1. From a dermatopathological point of view, if inclusion bodies are not observed, feline herpetic dermatitis can be indistinguishable from dermatitis caused by hypersensitivity reactions to stings or bites by arthropods and from the lesions of eosinophilic granuloma complex.
It may be useful to divide biopsy specimens of skin with a sterile scalpel and prepare slides for cytological studies by apposition of the cutting surface on the slide: these preparations can be used by the histologist both to search for inclusion bodies by staining with haematoxylin and eosin and to search for viral antigens with immunohistochemical techniques.
Polymerase chain reaction
If inclusion bodies are not detected, PCR can be carried out on tissues to reveal the presence of FHV-1 DNA. Real time PCR is currently considered the method of choice for identifying FHV-1 in biological samples since it produces greater amplification of the target sequences for recognition of the virus. This technique does, however, have some limitations. In fact, although real-time PCR analysis has been reported to have both high specificity and sensitivity for herpetic dermatitis, a positive result does not distinguish between active and latent infections or, using the standard procedures, the presence of vaccine DNA. Furthermore, increasing the sensitivity of the test increases the possibility of false positive results. Real-time PCR analysis of serum, conjunctival samples or oropharyngeal samples is not useful for diagnostic purposes in herpetic dermatitis, since many subjects come into contact with the virus in the early months of life and can carry it in a quiescent form.
Immunohistochemistry
Although this method is less sensitive than real-time PCR, it may be of greater utility since it is more specific. Through the use of virus-specific antibodies, the presence of some viral proteins that are expressed during active transcription of the virus can be detected in the tissue: this enables latent infections to be distinguished from active ones and the presence of the virus to be associated with the cutaneous lesions. However, a negative result does not allow a viral aetiology of the lesions to be excluded since the replicative activity of FHV-1 can be low in chronic forms of infection and not, therefore, always demonstrable.
TREATMENT
Skin lesions caused by FHV-1 can be difficult to cure and the prognosis is uncertain. There is not yet a single, recognized treatment, but there are various therapeutic options that can help to manage the problem. L-lysine, which inhibits the replication of Herpesvirus by reducing the bioavailability of arginine, an essential amino acid, may be effective at a dose of 200-500 mg/cat per os every 12-24 hours for at least 4 weeks. Interferon alpha, a cytokine with antiviral properties, has also been used to treat this viral dermatitis. The doses reported in the literature vary greatly; a dose of 30 U/cat/die per os in alternate weeks is the most widely used regimen for cutaneous infections. The use of interferon omega was described in one case report: the cytokine was administered both subcutaneously and perilesionally (0.75 MU/kg SC + 0.75 MU/kg inoculated into the perilesional area on day 0; 1.5 MU/kg SC on days 2 and 9; and then the same day 0 drug administration was repeated on days 19, 21 and 23). Of the various anti-herpetic drugs, acyclovir has scarce in vitro activity against FHV-1 and low bioavailability in the cat, while famciclovir was recently reported to have been effective in four cats with herpetic dermatitis: the therapeutic protocols used differed, ranging from 62.5 mg/cat per os every 12-24 hours to 125 mg/cat per os every 8 hours for 3-4 weeks. In three subjects the lesions recurred once the treatment was suspended. Glucocorticoids should not be administered either topically or systemically to cats with herpetic dermatitis.
Suggested readings
- Gaskell R, Dawson S, Radford A, Thiry E. Feline herpesvirus. Vet Res 2007, 38: 337-54.
- Gutzwiller ME, Brachelente C, Taglinger K, et al. Feline herpe dermatitis treated with interferon omega. Vet Dermatol 2007, 18: 50-4.
- Hargis AM, Ginn PE, Mansell JE. Ulcerative facial and nasal dermatitis and stomatitis in cats associated with feline herpesvirus 1. Vet Dermatol 1999, 10: 267-274.
- Holland JL, Outerbridge CA, Affolter VK, Maggs DJ. Detection of feline herpesvirus 1 DNA in skin biopsy specimens from cats with or without dermatitis. J Am Vet Med Assoc 2006, 229: 1442-6.
- Malik R, Lessels NS, Webb S, et al. Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. J Feline Med Surg 2009, 11: 40-8.
- Persico P, Roccabianca P, Vercelli A, Cornegliani L. Le infezioni cutanee da herpesvirus nel gatto: aspetti patogenetici, manifestazioni cliniche e metodiche diagnostiche. Veterinaria 2009, 3: 25-32.