Calicivirus: gingival and systemic disease

Transcription

1 Vet Times The website for the veterinary profession Calicivirus: gingival and systemic disease Author : MARTIN ATKINSON Categories : Vets Date : March 31, 2008 MARTIN ATKINSON concludes his two-part series on feline calicivirus with a discussion of its role in cases involving gingivostomatitis and virulent system disease PART one of this series (Veterinary Times, March 24 issue) on feline calicivirus (FCV) looked at the classical disease, treatment, vaccination and the carrier state. This second part discusses the role of FCV in gingival disease and the emergence of virulent systemic disease (FCV-VSD), and presents some revealing conclusions. Gingivostomatitis/ faucitis involving calicivirus infection Chronic gingivostomatitis is one of the more distressing and frequent sequelae of FCV infection. Up to 85 per cent of cats with chronic gingivostomatitis have been shown to be shedding FCV; therefore, the role of FCV should be considered in all cases of intractable dental disease. This is less likely to be a result of infection in naive cats than a progression of carrier status. Symptoms may be apparent almost as soon as the permanent dentition appears, and may present as lowgrade gingivitis that seems to cause the patient no apparent discomfort. However, this is likely to eventually progress through a variety of worsening scenarios to severe plasmocytic lymphocytic gingivostomatitis/ faucitis (PLGSF), which can be a very painful condition and the patient may be unwilling to eat (Figure 1). The progress to a debilitating disease is slow and may not be severe until it is accelerated by contributory dental disease. 1 / 17

2 In older cats, renal disease may increase the severity of the gingivitis and oral ulceration, and FIV or FeLV may be implicated in some cases. Up to 15 per cent of cats with PLGSF have been shown to be FIV and/or FeLV positive, and retroviruses should always be considered in the diagnostic work-up, especially in younger cats in high-risk groups with severe symptoms. Because a number of asymptomatic cats will be carriers of FCV, and recent research has shown that juvenile gingivitis due to tooth eruption can persist beyond 12 months, it is difficult to be certain of the role of FCV in cases involving juveniles. It is the author s opinion that it should be routine practice to test for FCV virus involvement by oral swabbing for virus isolation in young cats with persistent symptoms of gingivitis occurring at an earlier age than they would normally be expected. Good dental hygiene is paramount in the treatment of PLGSF and dental prophylaxis should be encouraged. However, alleviation of symptoms in the early stages and, indeed, slowing of the progression of the disease process may be achieved again with the use of feline recombinant interferon. FCV-positive cats can be treated with a combination of parenteral or intra-lesional injection and oral treatment, depending on the severity of symptoms on presentation (see and text on page 26). With just the use of oral interferon, a good response may be expected in cats that have minimal symptoms, and progression of dental disease may be delayed. Use of oral chlorhexidine solution and gels may also be beneficial. Unfortunately, although the author s experience with the use of interferon in the treatment of less severe cases has been encouraging, the response has been disappointing in more advanced cases. This is undoubtedly because the disease is multifactorial, involving viral and bacterial components plus the presence of plasmocyticlymphocytic disease in a number of cases indicates an immunemediated process, emphasising the complexity of the disease process (). Interesting recent research has shown that virus isolates from cats with FCV exhibiting gingivitis did not induce gingival disease directly in naive cats, but caused classical FCV symptoms thus, further emphasising the likely involvement of an immune mediated component in chronic cases. Although medical treatment may lead to remissions in symptoms, in many severe cases of PLSGF there ultimately appears to be little choice other than to perform radical dentistry, which may involve total extraction of the premolars and molars. It is often possible to leave the canine teeth and incisors, as they are less frequently involved so severely in the disease process. In the author s experience, after radical dentistry, and once the residual inflammation and infection has responded to antiinflammatory and antibiotic treatment, the worst of the gingivitis and faucitis appears to subside and the patient seems to tolerate minor residual inflammation, even if a complete cure is not apparent visually. 2 / 17

3 Although cat owners and clinicians are often reluctant to resort to such radical dentistry, in practice it is well tolerated as the reduction in symptoms more than compensates for the loss of dentition, and the change in the cat s demeanour can be rapid and dramatic. Because of the loss of alveolar and periodontal integrity, the extractions are usually relatively straightforward. If there is any doubt about whether radical extractions are necessary, the author recommends initially extracting one or two of the worst affected teeth. If they extract easily, it is usually the case that all the teeth will be in a similar predicament and total extraction is probably indicated. It is important not to leave any root fragments and to trim alveolar bone to below the gingival margin. However, because of the ease of root elevation, it is much less likely that the roots will fracture and be retained. If the periodontitis is not too severe and root attachments are sound, the disease process is probably not too advanced and good dental hygiene and conservative treatment may continue to be successful. Rare severe cases that remain refractory to management, even with radical dental treatment, may require antibiotics, interferon and anti-inflammatory treatment (long-term antibiotic treatment and depot injection, or long-term oral medication with corticosteroids). The author believes that although corticosteroids may bring about a marked temporary alleviation of symptoms, long-term corticosteroid therapy should be a treatment of last choice and should not be considered until clients have been fully advised as to the risk of side effects and/or where other modalities are not an option. FIV-positive cats appear to be over-represented in this group of poor responders and, although the use of corticosteroids in animals that are already immunocompromised may logically be contraindicated, the immunemediated disease that appears to be associated with the FIV/FCV complex does seem to respond. Given the limited treatment options for these cats, this may, in any -). case, be an option of last resort and there is generally little to lose ( FCH-associated virulent systemic disease It is generally considered that classic FCV infection does not cause serious disease, such as FHV, and that most kittens recover leaving the likelihood of entering a carrier status as the most common sequel. However, a number of outbreaks as long ago as 1998 in the USA, but since 2003 in the UK have seen the emergence of a more virulent form of the disease with much higher mortality rates approaching 50 per cent. In the USA, these outbreaks appear to have primarily started with a cat 3 / 17

4 from a rescue centre and subsequently clustered on veterinary practices. They are still rare but their frequency is increasing. The outbreaks have involved vaccinated as well as naive cats and it appears that we are seeing the emergence of more pathogenic strains of FCV with novel antigenic properties, against which most current FCV vaccines are unprotective. However, in one outbreak reported in a multi-cat environment in the UK with a mixed population of vaccinated and unvaccinated cats, the vaccinated cats suffered lower morbidity and mortality. Vaccination with a small number of viral subtypes may have preselected other more virulent strains, as may high levels of non-neutralising antibody in situations with high population densities. Stress due to overcrowding undoubtedly plays a part in this disease s development. The outbreaks of FCV-VSD in the USA and in the UK appear to be unconnected. So far, they have all been self limiting and died out within two months. One important difference between these outbreaks is that staff in the USA have been shown to have transmitted virus to cats outside the confines of their workplace; this does not appear to be a significant issue in the UK yet. In several outbreaks in catteries and veterinary hospitals in the USA reported by the University of California Davis a mortality of up to 40 per cent was observed, with a higher rate in adults than kittens. Incubation was typically one to five days, but was up to 12 days in some cases, with a course of four to nine days; transmission is thought to have been through faeces and from skin lesions in addition to the normal routes. FCV-VSD is characterised by epithelial cell cytolysis and systemic vascular compromise similar to that seen with the rabbit calicivirus, viral haemorrhagic disease. Symptoms of typical respiratory disease may be seen in about half of cases. Other common symptoms include: sudden death with minimal visible symptoms; marked pyrexia; facial and limb oedema; and ulceration and hair loss on the face, feet and pinnae (). Less consistent symptoms of FCV-VSD include: dyspnoea due to pneumonia; vomiting and diarrhoea; 4 / 17

5 jaundice; ascites; pancreatitis; and bleeding disorders. Laboratory findings include: moderate hypoproteinaemia; raised Tbil and CK; a mild neutrophilia and lymphopaenia; and a non-regenerative anaemia. Differential diagnoses include feline pox virus and immunemediated disease, but neither will be as acute or severe; nor will they have such a high morbidity. Postmortem findings include: peracute hepatic necrosis; epithelial necrosis/ulceration; variable involvement of other viscera, including necrotic lesions in the lungs, pancreas, spleen and gastrointestinal tract. The study team isolated viral antigen from the epithelial tissues, lungs and pancreas but not from the liver, spleen or lymph nodes. The lesions in these organs may reflect the result of immunemediated vasculitis, rather than direct involvement of the virus. The researchers at UC Davis were at pains to point out that these symptoms may be present in a number of other diseases and are not diagnostic of FCVVSD. As FCV may be found on oropharyngeal swabs in a proportion of healthy cats, and as there is no test that can distinguish FCV-VSD from less virulent field strains, other factors need to be present to make a diagnosis of FCV-VSD. This would probably need to include the involvement of several cats in a hospital or cattery, and isolation of virus from serum and tissue samples to increase the index of suspicion. Some of these postmortem changes may be mimicked by feline infectious peritonitis (FIP), but histologically the lesions are likely to reflect necrotic vasculitis rather than +the more chronic granulomatous changes seen in FIP. Furthermore, FIP is likely to run a much longer course and, 5 / 17

6 similarly, will have a lower morbidity. However, it remains a consideration in individually affected cats where FIP would normally be the primary differential from postmortem examination. Identification of the causative virus by immunofluorescence performed on appropriate tissue samples may be diagnostic. As these known outbreaks of FCH-VSD have affected vaccinated and naive cats, methods other than vaccination must be used to aid control. Control of transmission through fomites with thorough cleaning, strict antisepsis and barrier care should also be instigated. Many disinfectants are known to be ineffective against FCV, but bleach (sodium hypochlorite) diluted at 1: 32 with water and detergent, and potassium peroxymonosulphate (PMS) have been used effectively. PMS has the added advantage that it is still effective in the presence of organic debris. It should also be recognised that asymptomatic carriers and mildly affected individuals can also transmit virulent disease to susceptible cats, and all cats in contact with an outbreak should be tested for FCV. Conclusions FCV has been shown to evolve within individual cats and in colonies. This has important implications, not only for the disease, but also for attempts to control it with vaccination. FCV-VSD should be considered as a differential diagnosis in any severely ill cat, especially when dealing with disease outbreaks in multicat environments. Recombinant feline interferon is increasingly used in the treatment of viral diseases in cats, even though much of this is off-licence, and this product seems to have a role to play in acute and, to a lesser extent, chronic FCV infection. Despite their limitations, existing vaccines still appear to be effective at controlling the majority of clinical disease. However, some concerns remain, including failure to achieve full immunity, apparent vaccine breakdowns and live vaccine-induced disease. There is a need for future research and development to include broadening the crossreactivity of vaccines to field viruses especially the recently evolved highly virulent strains and for finding ways of reducing virus shedding in cats vaccinated with live vaccines. The improvement of vaccines based on new virus strains is encouraging. References and further reading Hurley K F, Pesavento P A, Pedersen N C, Poland A M, Wilson E and Foley J E (2004). An outbreak of virulent systemic feline calicivirus disease, JAVMA 2(224): Pesavento P A, MacLachlan N J, Dillard- Telm L, Grant C K and Hurley K F (2004). Pathologic, immunohisto- chemical and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats, Vet Pathology 41: ACVP. 6 / 17

7 Chandler E, Gaskell C and Gaskell R (1995). Feline Medicine and Therapeutic, Blackwell. Radforda A D, Dawson S, Coyne K P, Porter C J and Gaskell R M (2006). The challenge for the next generation of feline calicivirus vaccines, Veterinary Microbiology 1(117): De Mari K (ed; 2004). Veterinary Interferon Handbook (1st edn), Virbac. Day M J, Horzinek M C and Schultz R D (2007). Guidelines for the vaccination of dogs and cats: compiled by the Vaccination Guidelines Group of the World Small Animal Veterinary Association, Journal of Small Animal Practice 48(9): TerWee J, Lauritzen A Y, Sabara M, Dreier K J and Kokjohn K (1997). Comparison of the primary signs induced by experimental exposure to either a pneumotrophic or a limping strain of feline calicivirus, Veterinary Microbiology 1-2(56): Other references are available on request. Special acknowledgment to Tim Gruffydd Jones, of The Feline Centre, University of Bristol. USE OF INTERFERON FOR FCV GINGIVITIS AN oral solution of interferon can be made up by reconstituting and diluting 10 mega-units (MU) of recombinant omega interferon of feline origin in 200ml sterile saline, which will give a solution of 50,000 units per millilitre. This solution can be frozen for several months in aliquots of 10-20ml. Thawed solution should not be re-frozen, if possible, but can be stored for up to three weeks in a refrigerator. Smaller aliquots make it more practical to avoid repeated thawing/refreezing cycles and to minimise repeat contamination of the solution on withdrawal. A daily dose of 1ml should be given orally, either directly into the mouth by syringe or dropper, or in a very small amount of fish juice or similar. It should not be added to food or water as this will cause too great a dilution. In the author s experience, the solution is well tolerated orally. Due to continual shedding of FCV, it may be necessary to continue oral medication indefinitely. Intralesional injections can be achieved by reconstituting a 10MU vial in 1ml of diluent and dividing this between the oral sites approximately 0.1ml in up to 10 sites. Try to avoid injecting into severely compromised tissue, but aim for adjacent viable tissue. The recommended dose for parenteral treatment of FCV gingivitis is 1MU/kg subcutaneously every other day for five injections. This may be repeated where a regression is seen following initial response to treatment. 7 / 17

8 Figure 1. Plasmocytic lymphocytic faucitis. 8 / 17

9 Figure 2. Progression of treatment modalities for FCV-related gingivostomatitis. 9 / 17

10 Figure 3. Gingivitis may be associated with FCV and can respond well to oral interferon treatment. 10 / 17

11 Figure 4. Severe gingivitis associated with FCV and dental disease. 11 / 17

12 12 / 17

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14 Figure 5. Visible signs of gingivitis and faucitis sometimes persist post-treatment, but cats seem to tolerate this well. 14 / 17

15 Figure 6. Post-eruption gingivitis may persist for up to 12 months. 15 / 17

16 Figure 7. Facial oedema and ulceration are common symptoms of virulent systemic disease. Typical symptoms of respiratory disease are also common, and patients may present with pyrexia and hair loss. 16 / 17

17 TABLE 1. Rationale for routes of administration of interferon for FCV gingivitis 17 / 17 Powered by TCPDF (