FIV and
Feline Lymphocytic-Plasmacytic Gingivostomatitis
(LPGS)
_________________________________________________
Characteristics, Causes, Diagnosis
Medications and Supplements
Treatment
References
_______________________________________
Characteristics, Cause, and Diagnosis
1. Characteristics
2. Causes
3. Diagnosis
1. Characteristics
Feline Lymphocytic-Plasmacytic Gingivostomatitis (LPGS), by whichever of its many names it goes, is an
oral inflammatory disease that is recognized or will be recognized by most of the owners of about half of
all cats infected with FIV that suffer from chronic oral inflammatory disease. It is easily the most common
secondary problem associated with FIV infection, occurring particularly in middle-aged or old cats [Wolf],
and is almost universally characterized as difficult to treat with lasting success.
Chronic Gingivitis in the Cat [Judy Zinn, DVM]
Plasmacytic-Lymphocytic Stomatitis in cats is a chronic condition that results in extreme gingivitis and
tooth loss. . . . Cats with stomatitis often have a rancid odor in their mouth, salivate excessively and have
difficulty eating. The chronic mouth pain results in a decreased appetite and weight loss. Examination of
the teeth and gums reveals extreme gingivitis especially around the upper back molars. The gums will
appear raw and bumpy and bleed easily. As the disease progresses the gums will recede from the tooth
root and the root will begin to be absorbed resulting in tooth loss. . . .With this degree of inflammation
occurring, secondary invasion of bacteria is very common. The bacterial infection results in the rancid
odor. . . .
http://www.winnfelinehealth.org/health/gingivitis.html
PLUGS: Cats in the Trenches [Elaine Cebuliak B.V.Sc., Dip.Ed.]
PLS is seen as a severe inflammation of the mucosa, fauces and gingiva of the oral cavity; often causing
proliferation of gingiva, intense pain, halitosis, ptyalism, anorexia, lethargy and behaviour changes. There
are various degrees of inflammation present, and the distribution within the oral cavity usually is more
severe from the upper second premolar distally toward the fauces.
http://www.ava.com.au/aahv/ArticlespracPlugs.html
Feline Stomatitis [All Pets Dental Clinic]
Many cats affected by LPS will be unable to eat, develop weight loss, and have excess salivation. Oral
examination often reveals a "cobble stone"-like redness in the throat area and severe inflammation where
the tooth and gums meet. The premolar and molar areas are usually affected more than the canines and
incisors. Intraoral x-rays often reveal moderate to severe periodontal disease. In addition to generalized
inflammation, all stages of feline ondontoclastic resorptive lesions may be present.
http://www.dentalvet.com/vets/cats/feline_stomatitis.htm
Inflammation may occur in the gingiva [gums], the fauces[back of the mouth], the buccal [cheek] mucosa,
even the tongue. The site of inflammation often provides the part of the terminology of diagnosis and may
also indirectly indicate the seriousness of the infection. Faucitis would indicate inflammation of the area
between the soft palate and throat. When tissue is biopsied, the results of the biopsy often show
"lymphocytic-plasmacytic stomatitis." In other words, the two lymphocyte types of the specific immune
response are present in abnormal numbers.
Not all feline inflammatory oral disease is LPGS. Many cats will suffer from treatable periodontal disease.
LPGS itself is a blanket term to describe a condition that may proceed from different underlying
conditions. Not all cats with LPGS suffer from immunosuppressive viral disease. A number of sources
[e.g. Addie, Wolf] insist that LPGS is not particularly associated with FIV infection and is distributed
throughout the feline population--a conclusion that begs the question of why half of all FIV+ cats suffer
from significant oral inflammation when half of FIV- cats don't and why other studies found a clear
correlation. A 1993 study of a colony of mixed FIV+ and FIV- cats reported, "The gingivitis was generally more severe in the cats infected with both [calici and feline immunodeficiency] viruses, suggesting that feline immunodeficiency virus may make cats infected with calicivirus more susceptible to chronic gingivitis"[Waters]. A 2006 study of nearly nine thousand cats found that cats with retroviral infection (FIV and
FeLV) suffered from oral disease generally and stomatitis in particular at many times their representative
percentage of the feline population [Bellows2]. While immune suppression appears to be a factor in
expression of the disease, immune hyperactivation is at least as important a feature. A more
comprehensive view might be this one offered by Judy Rochette: "The oral tissues are constantly exposed
to bacterial pathogens and antigenic proteins. In a healthy mouth, a balance is maintained between
progression of disease and the host's immune system. Humoral and cellular immunity invokes the presence in the oral tissues of neutrophils,
lymphocytes, plasma cells, interleukins, cytokines, prostaglandins, histamine, complement, kinins, helper
and suppressor T-cells, natural killer cells, and antibodies. Any imbalance in the interactions involved in
this complex protective mechanisms results in a disease state. Both inadequate and exuberant host
responses have been identified as causes of stomatitis." In FIV+ cats, the skewing of immune response
is already a feature of the disease, which is perhaps a reason why acquired LPGS seems particularly
refractory in them.
2. Causes
Not only is the underlying cause of LPGS unknown, but there is a general belief that a complex of causes
are involved. Veterinary dentists seem inclined to approach the problem from a more narrowly dental
point of view, emphasizing interaction of teeth and tooth environment. Veterinary nondentists tend to see
the problem more broadly, emphasizing the state of immune response. A number of characteristics are
seen in case after case, but part of the problem lies in deciphering which characteristics are causes and
which are effects of prior causes.
Bacterial Infection. Gram-negative anaerobes present in plaque are thought to be a major contributing
factor to LPGS [Klein]. According to some dental vets, most cases of feline gingivitis/stomatitis syndrome
involve an exaggerated oral immune system response to these plaque bacteria and perhaps others
[Carmichael]. Other vets argue, however, that this explanation is too narrow and does not explain the
presence of lesions in other sites of the oral cavity. One writer has noted that the bacteriods found in the
oral tissue of felines with severe LPGS are similar to those found in humans and canines with milder
gingivitis, suggesting that there is something peculiarly exaggerated about the feline reaction to them
[Cebuliak]. FIV+ status may make a difference in the bacterial aspect of LPGS, at least in regard to some
aerobic bacterial populations. Healthy cats with gingivitis/stomatitis without FIV have different strains of
Staphylococcus sp. than cats with FIV. Moreover, cats with gingivitis and infected by FIV have higher
numbers of bacteria compared to those not infected by FIV and Corynebacterium sp. Streptococcus sp.,
Proteusmirabilis sp., Klebsiella pneumoniae and Pseudomonas sp. predominate, a significantly different
population of gingival bacterial population than found in cats without FIV, possibly because immune
suppression creates a greater susceptability to opportunistic infective organisms [Daniel].
Viral Infection. There is a generally held belief that a major component of LPGS in many or most casesis antigenic stimulation of immune response caused by chronic, carrier-state infections. Feline calici virus
infection is widely accepted as playing a major role in much LPGS; feline herpesvirus has a more
ambiguous association, but seems clearly involved in some feline inflammatory oral disease. In one
study, eighty-eight per cent of cats with chronic gingivostomatitis were shedding both viruses, compared to
21% of cats without [Lommer]. Cats with chronic gingivostomatitis are significantly more likely to
concurrently shed both feline calicivirus and feline herpesvirus than are cats with classical periodontal
disease. Feline herpesvirus has been documented as associated with a unique ulcerative and often
persistent facial dermatitis or stomatitis syndrome. This syndrome is believed to be relatively common
[Hargis]. Calici virus has been isolated in near 100% of chronic gingivostomatitis cases in some studies.
Primary calici infection is itself associated with a transient and recognizable stomatitis. However, the
chronic carrier state sees the emergence of antigenically distinct and distant viruses from the infective wild
type [Poulet] and may therefore have a unique disease causing role in the emergence of LPGS, although
this premise has been called into doubt [Southerden]. FIV, however, introduces a separate element in the
LPGS equation. A 1991 Cal Davis study found that while cats infected with calici virus alone did not have
a higher likelihood of developing inflammatory oral disease than other cats, those cats coinfected with FIV
and FCV had the highest prevalence of oral cavity infections and the most severe lesions [Tenorio]. In a
British study, 92% of chronic stomatitis cases in a hospital setting (79% in general practice) tested
positive for calici virus, compared to 19 per cent of controls in both cases. In the same study, FeLV
prevalence was low in all chronic stomatitis populations, but a significantly higher prevalence of antibody
to FIV was found (81 per cent) compared with time-matched controls (16 per cent) [Knowles]. The
prevalence of LPGS in FIV+ cats coinfected with other viruses, particularly calici virus, may involve the
double whammy of chronic antigenic stimulation by a carrier-state infection and both immunosuppression and a characteristically skewed immune response
associated with FIV infection. FIV has been shown to result in more serious acute infections of calici and
herpes; perhaps it is also responsible for a more pathogenic carrier state.
[***Bartonella***]. A virus-like antigen-stimulating role has been suggested in recent years for the
bacterium Bartonella henselae. "Feline Bartonella are Gram-negative bacilli that possess pili which are
hair-like structures found on the bacteria’s surface. Bartonella have a strong tendency to stick or clump
together in tissues and in culture and to stick to, and penetrate, RBCs and endothelial cells. . . . The ability
to adhere to each other, and to the membranes of RBCs and endothelial cells, leads to the wide and
varied tissue pathogenesis observed in cats, dogs and people. Pili and a protein called deformin are
probably responsible for the sticky properties. The wide tissue specificity of Bartonella is due to the
adhesion to endothelial cells which are the constituents of capillaries. Experimental data show that B.
henselae interaction with macrophages . . . induce[s] proliferation of endothelial cells. Bartonella proteins
stimulate endothelial cells to proliferate causing neovascularization or angiogenesis and an outpouring of
inflammatory cytokines which recruit inflammatory cells such as lymphocytes,plasma cells and
macrophages. Thus, Bartonella induce chronic lymphocyticplasmacytic granulomatous inflammatory
reactions in highly vascular tissues throughout the infected animal’s body" [Hardy] . The mounting
"evidence" for Bartonella involvement in LPGS and other feline illnesses has its naysayers. One skeptic
has questioned why, if a bacterium is responsible for the underlying problem, antibiotics are not able to
eradicate it [Wolf1]. According to Alice Wolf, “Recent studies by Dr. Mike Lappin and the infectious
disease group at Colorado State University have shown no statistical differences in Bartonella
seropositivity between cats with and without uveitis, oral cavity disease, and central nervous system
disease (ACVIM 2005)” [Wolf2]. Since Bartonella DNA can be recovered from cats who have 'cleared"
the infection, according to available tests, the book is still being written on what Bartonella does and does
not do.
Immune Dysfunction. Hyperstimulation, dysregulation, and loss of immune response have all been strongly implicated in LPGS. In one study, the cats with LPGS "tended to demonstrate generalized and progressive up
regulation of cytokine expression as the lesion severity increased. The similarity of the cytokine profile in
lesions from different cats supports the view that a similar pathogenesis underlies all cases." Cytokines
are immunoregulatory proteins commonly secreted by T-Helper 1 [cytokines IFN-γ, IL 2, IL-12]and T-Helper 2 [Cytokines IL-4, IL-5, IL-6, IL-10] lymphocytes. TH-1 cytokines predominate in healthy feline oral
tissue. Cats with LPGS show a mixed TH-1/TH-2 pattern. "IFN-γ, IL-2, IL-12 . . ., and IL-10 were
detected in the majority of nondiseased faucal-tissue samples. In contrast, IL-6 was found in only a small
proportion of the samples, while neither IL-4 or IL-5 was detected in any samples from nondiseased
analysis. . . . In contrast, the relative levels of IL-2, IL-4, IL-6, IL-10, IL-12 . . . ,and IFN-γ mRNA
expression were all significantly higher in the diseased population. . . . The results also suggest that IL-6
expression is induced early in the pathogenesis of the disease,whereas expression of IL-4 is a late event
and is mainly confined to established lesions. This would imply that the underlying immunological bias
switches from a predominantly classical type 1 to a mixed type 1-type 2 response as the lesion
progresses" [Harley1]. It should be noted that this type of T-lymphocyte skewing is characteristic of LPGS
cats generally. However, the class shift from type 1 to type 2 bias is also characteristic of FIV infection.
The extent to which these twin biases might have a multiplier effect has gone uncommented on.
Abnormalities in antibody production have also been noted in cats with LPGS. "The cats with chronic
gingivostomatitis had significantly higher salivary concentrations of IgG, IgM and albumin, and higher
serum concentrations of IgG, IgM and IgA, but significantly lower salivary concentrations of IgA than the
healthy cats" [Harley2]. “ IgA neutralises pathogens and toxins inthe oral cavity, inhibits the adherence
or growth of microorganisms on the oral mucosa or teeth and enhances non-specific defence factors. It is
unclear whether the Ig pattern described is a cause or a result of the inflammatory disease” [Southerden]. Evidently a dearth of T-Helper cell numbers rather than type-bias is responsible for a recently observed excess of IL-8 in lesions of FIV+ cats with severe oral inflammation [Zuccari]. Both FIV and HIV infections, it has been noted, result in defective neutrophil development. “. . . we observed that neutrophils from HIV-infected patients have a profound defect in chemotaxis in response to endogenous (IL-8) . . . which was directly correlated with peripheral CD4+ [Helper-T] lymphocyte levels.” Chemotaxis in this case refers to the ability to respond to recruitment cues. “A similar chemotactic defect was observed in the feline immunodeficiency virus (FIV) model of HIV infection” [Heit]. Neutrophils, as major antibacterial immune cells, are essential to control of pathogenic oral bacteria
Dietary Allergy/Sensitivity. Although there have been no studies to confirm it, there is a long-standing
suspicion that elements of prepared feline diets play a role in feline LPGS. Human studies have
confirmed that certain dietary substances can cause or worsen oral inflammation. What the offending
substances might be in cats is speculative. Canned and dry cat foods have a variety of additives intended
to enhance flavor (e.g., cinnaminase/ cinnamaldehyde and benzoin), consistency, and freshness. Grain products have
often been singled out for attention in the case of feline bowel disease and could conceivably have a role
in feline oral disease. Retrospective examination of feline skulls from museum collections revealed in one
study a much lower incidence of FORLs (resorptive, or "neck," lesions caused by immune attack on the
tooth) prior to 1960 than is the case today [Klein]. FORLs have a known connection to FIV+ status [Hofmann-Lehmann], may
and probably will occur concurrently with LPGS, but are a separate pathology. The researchers have speculated that either dietary changes or vaccination protocols are the most obvious areas to look for an
explanation. Several successful treatment programs have involved carefully controlled dietary intake, but
since other therapies were used concurrently, they provide no "smoking gun" that dietary change by itself
is significant. Diane Addie does mention,"In addition, after dentistry, cats fed on Hills a/d diet gained more
weight and had smaller lesions than those fed on a control diet (Theyse et al, 2003)." The reference is to
a field study presented at the Hills European symposium on Oral Care, Amsterdam, 2003. The study is
unavailable for inspection.
3. Diagnosis
Diagnosis, properly done [Carmichael], is likely to be at least a two-part process involving two visits to the
vet.
First Visit:
● A thorough physical exam, including examination of the teeth and oral cavity for evidence of tartar,
for location of any FORLS (with particular attention to those that may be hidden by overgrowth of
inflamed gingival tissue), and for notation of the location of any sites of inflammation and
inflammatory lesions. "Many of the more severely affected cats will have very proliferative and
painful hyperplastic tissue in the fauces of the mouth. Lesions are usually bilateral which will help
to distinguish this condition from neoplasia" [Wolf1]
● A CBC and serum chemistry. In the case of LPGS, hyperglobulinemia (overactive antibody
response) is a common finding in the serum chemistry. (It is also a common finding in serum
chemistries of FIV+ cats generally, indicating a hyperactive antibody response to the virus.)
● If evidence upon examination suggests a significant pattern of inflammatory disease, FIV and
FeLV testing will be done, unless the cat's status in this regard is already known.
● A return visit scheduled for further examination and dentistry and dental prophylaxis under anaesthesia.
Second Visit:
● Polishing and scaling under anaesthesia. Any teeth that need to be removed will be removed.
● Radiographs taken (if teeth have been removed) for any evidence of root tips and fragments.
● Individual biopsy samples taken from lesions at sites of inflammation and sent off for analysis.
One writer cautions of the importance of retrieving samples from deeply rather than superficially in
the lesion.
The Biopsy Analysis
Analysis is likely to return a finding of lymphocytic plasmacytic stomatitis. However, it is necessary to
eliminate results that might alter treatment: e.g.,eosinophilic granuloma, autoimmune diseases such as
pemphigus, several types of cancer [Carmichael], or cyrptococcosis [Cebuliak]. As can be seen in the
following example, biopsy results can also provide cues for possible future developments that will require
close monitoring.
Example
Following is a case history demonstrating the diagnostic procedure
"A 12-year-old, neutered male, domestic shorthair was presented due to difficulty in eating, pawing at
the face, and weight loss. Three years earlier, the cat had undergone a dental prophylaxis for mild
gingivitis and tartar accumulation. On physical examination (day 1), mild dental tartar, severe gingivitis,
and stomatitis involving the caudal part of the dental arcades, the commisures of the lips, and under the tongue on both sides were apparent. A complete blood (cell) count (CBC) and serum biochemical profile
revealed mild decreases in albumin and alanine aminotransferase (ALT). An enzyme-linked
immunosorbent assay (ELISA) (SNAP FeLV/FIV antigen test; IDEXX, Toronto, Ontario) was negative. . . .
"On the day of surgery . . . the cat was maintained under general anesthesia with isoflurane (Isoflurane;
Vetoquinol) in order to perform a dental scaling and gingival biopsy. A complete scaling and polishing was
performed on all of the teeth. Two teeth, numbers 309 and 409, were extracted. Although teeth numbers
107, 108, 207, 208, 308, and 408 were not removed at this time, a note was made to examine the gingiva
around these teeth biannually for a worsening or improvement of the current clinical presentation. Two 5-mm by 5-mm biopsies were taken from an area of gingival hyperplasia in the right ventral quadrant. The
biopsy samples were preserved in 10% buffered solution and sent for histopathologic examination
(Histovet, Guelph, Ontario). Histological examination of these samples revealed marked hyperplasia of the
gingival epithelium with severe inflammation of the lamina propria. Some areas of each biopsy contained a
predominantly lymphoplasmacytic infiltrate, while others showed significant eosinophilic inflammation.
Focal areas of epithelial dysplasia were evident, as well as suppurative lesions associated with gingival
ulceration. The lesions were considered consistent with the syndrome known as lymphoplasmacytic
stomatitis (LPS). Eosinophilic inflammation is not only suggestive of hypersensitivity disease, but in
combination with the epithelial dysplasia, it has been shown to predispose to subsequent development of
carcinoma" [Baird].
Chronic Pathogens
Given the evidence implying a role for chronic pathogens in the pathology of LPGS, there is a superficial
case to be made for extending the diagnostic procedure to testing for the presence of these pathogens.
Bartonella testing has, evidently, become more common in clinical practice. This may, in part, be because
it is treatable with antibiotic therapy. However, Bartonella is frequently a relapsing infection, and no single
test, antibody or PCR, can guarantee that the organism has been cleared. The various treatment
protocols for Bartonella are not dealt with in this file because they are complex and involve many
uncertainties. Four-week courses of azithromycin are the most common prescription.
Testing of various sorts is also available for herpesvirus and calici virus. Since therapy for these viruses is
either cheap and nonintrusive (as with lysine for herpesvirus) or expensive,difficult to access, too
potentially immunosuppressive, or helpful for treatment of LPGS regardless of underlying viral pathogens,
practitioners may decide that testing is not warranted. Certainly, it does not seem to occur much. The
wisdom of such testing is a matter best left to individual discussion between client and veterinarian. Addie-Radford proposed, on the basis of their one-cat study model, testing repeatedly for calici virus during the
course of feline interferon therapy, when the object is to eradicate the virus. How adaptable their
laboratory model is to an actual clinical situation is hard to say. Idexx laboratory, which has a new PCR
program using the Taqman DNA PCR system, now offers reasonably priced assays for herpes and calici
viruses individually, as well as a one-price panel for all of the major upper respiratory viruses: herpes,
calici, chlamydia, bordetella, and mycoplasma.
>>>Medications and Supplements (LPGS)>>>
