Known causes of chronic nasal discharge in dogs include neoplasia, foreign bodies, extension of oral disease (eg, tooth root abscess and oronasal fistula), and infectious disease (particularly mycosis and parasitism). Often, however, an underlying cause cannot be identified, and a diagnosis of nonspecific chronic rhinitis or lymphoplasmacytic rhinitis is made in 25% to 50% of dogs that undergo extensive evaluation for chronic nasal discharge.1,2 First described in 1987 in a report3 involving 5 dogs, lymphoplasmacytic rhinitis was initially thought to be a steroid-responsive disease. However, in a subsequent report4 involving 37 dogs with lymphoplasmacytic rhinitis, administration of antimicrobials and corticosteroids was often ineffective.
Because dogs with lymphoplasmacytic rhinitis may have neutrophilic inflammation of the nasal mucosa, in addition to the characteristic lymphoplasmacytic infiltration,4 less specific terms, such as chronic rhinitis, chronic inflammatory rhinitis, and idiopathic chronic rhinitis, have also been used to identify this condition. Determining the underlying cause of idiopathic chronic rhinitis in dogs could lead to more specific treatments, potentially improving the quality of life of affected dogs and their owners.
Members of the genus Bartonella are vector-transmitted, bloodborne, intracellular bacteria. Currently, their pathogenicity in dogs is incompletely understood.5 However, a study6 investigating associations between clinical signs and seropositivity against 3 Bartonella spp found that seropositive dogs were 10 times as likely to have a history of nasal discharge, including epistaxis, as were seronegative control dogs. Nasal discharge has also been mentioned as a clinical sign in several dogs with bartonellosis reported in the literature.7–9 It seems possible, therefore, that Bartonella infection may play a role in dogs with chronic rhinitis and that a diagnosis of bartonellosis has been overlooked in these dogs because of the relatively recent identification of these organisms as potential pathogens and because of the difficulty in confirming infection with Bartonella spp.
A previous retrospective study10 failed to find molecular evidence of Bartonella organisms in paraffinembedded tissues from dogs with idiopathic lymphoplasmacytic rhinitis. However, these findings did not rule out Bartonella infection as a possible underlying cause because rhinitis in infected dogs might develop secondary to systemic vascular infection or as a sequela of immune-mediated inflammation. The present study, therefore, was designed to use serologic and molecular techniques to determine whether evidence of Bartonella infection could be found in dogs with idiopathic chronic rhinitis. Specifically, the purpose of the study reported here was to compare prevalence of serum antibodies against Bartonella vinsonii subsp berkhoffii or Bartonella henselae and prevalence of Bartonella DNA in blood between dogs with rhinitis of any duration and in which no specific etiology had been found and age- and weight-matched control dogs without evidence of clinical signs known to be associated with Bartonella infection.
Materials and Methods
Dogs—Dogs with nasal discharge of any duration in which an underlying cause could not be identified on the basis of results of diagnostic imaging (nasal radiography or computed tomography), rhinoscopy, and histologic examination of nasal biopsy specimens were eligible for inclusion in the study. Medical records of case dogs included in the study were reviewed to determine the nature of the nasal discharge (ie, serous, mucoid, mucopurulent, or hemorrhagic), duration of the discharge, and histologic findings.
For each case dog, 1 or 2 control dogs matched on the basis of age (± 18 months) and body weight (± 5 kg [11 lb]) were included in the study. Dogs were considered for inclusion in the control group only if they did not have evidence of nasal disease or clinical signs believed to be associated with bartonellosis, including endocarditis, myocarditis, granulomatous disease, hepatitis, thrombocytopenia, lameness, and splenomegaly. In all but 1 instance, control dogs were patients of the same veterinary practice as case dogs. Signed consent was obtained from owners of all dogs included in the study.
Study protocol—The study protocol was approved by the North Carolina State University Institutional Animal Care and Use Committee. Blood samples were obtained from all case and control dogs enrolled in the study and submitted for serologic and molecular testing for evidence of Bartonella infection. Indirect fluorescent antibody assays performed as described11 were used to test sera for antibodies against B henselae and B vinsonii subsp berkhoffii antigens. A PCR assay performed as described12 was used to test blood samples anticoagulated with EDTA for DNA from all known Bartonella spp. Primers (5cAGA TGA TGA TCC CAA GCC TTC TGG3c and 5cGAT AAA CCG GAA AAC CTT CCC3c) designed to amplify an approximately 120-base pair portion of the internal transcribed spacer region common to all known Bartonella spp were used. Samples were tested for the presence of endogenous inhibitors by amplification of a glyeraldehyde-3-phosphate dehydrogenase pseudogene, as described.13
Statistical analysis—The Fisher exact test was used to compare results of serologic and PCR assays between case and control dogs. Analyses were performed with standard software.a A value of P < 0.05 was considered significant.
Results
Dogs—Forty-four dogs with idiopathic nasal discharge and 63 control dogs without nasal discharge or signs of disease associated with bartonellosis were included in the study. Mean age of the case dogs was 8 years (range, 6 months to 15 years), and mean body weight was 22.7 kg (49.9 lb; range, 4.5 to 52 kg [9.9 to 114.4 lb]). Mean age of the control dogs was 7.2 years (range, 1 to 14 years), and mean body weight was 25.4 kg (55.9 lb; range, 2.2 to 49 kg [4.8 to 107.8 lb]). Twenty-five of the 44 (57%) case dogs and 35 of the 63 (56%) control dogs were male.
For the case dogs, mean duration of nasal discharge prior to examination was 11 months (median, 7 months; range, 0.03 to 96 months). Nature of the nasal discharge was recorded in medical records for 40 of the 44 case dogs. Thirty-seven dogs had bilateral nasal discharge, and 3 had unilateral nasal discharge. The discharge was mucopurulent in 28 of the 40 (70%) dogs, hemorrhagic in 6 (15%), and serous in 2 (5%). The remaining 4 dogs had had 2 or more types of nasal discharge prior to examination.
Results of histologic examination of nasal biopsy samples were available for all 44 dogs. Fifteen dogs had lymphoplasmacytic rhinitis with suppurative inflammation; 13 had a combination of lymphoplasmacytic, suppurative, and eosinophilic inflammation; 11 had lymphoplasmacytic inflammation alone; 4 had suppurative inflammation alone; and 1 did not have any histologic abnormalities.
Results of serologic and PCR assays—Results of the serologic and PCR assays were negative for all 44 case dogs. One control dog had antibodies against B henselae (titer of 1:64). A second control dog had positive PCR assay results. We did not detect a significant (P = 0.51) association between assay results and group designation.
Discussion
The present study failed to confirm an association between Bartonella infection and idiopathic rhinitis in dogs. Evidence for infection with Bartonella organisms was low in both groups, with only 2 control dogs having positive assay results. By comparison, a previous study14 reported that 8.7% of healthy working dogs belonging to the US government were seropositive for antibodies against B vinsonii subsp berkhoffii. On the other hand, the proportions of dogs in the present study with evidence of Bartonella infection (0% of control dogs and 3% [2/63] of control dogs) were consistent with prevalences of anti-Bartonella antibodies reported in other studies.6,15 It is difficult to recruit sufficiently large study populations to statistically prove a lack of association. However, the fact that we did not find any evidence of exposure to or infection with Bartonella spp in 44 dogs with idiopathic nasal discharge suggested that Bartonella infection is not a common cause of this disease. As executed, the study had reasonable power (1 – E = 0.8) to detect a difference between groups of ≥ 20%, assuming that the prevalence of Bartonella infection in the control group was truly 3%. Nevertheless, our findings do not rule out the possibility that Bartonella infection may cause nasal discharge in some dogs.
Our failure to find an association between Bartonella infection and idiopathic rhinitis was consistent with findings of a recent report10 in which Bartonella DNA was not identified by means of a PCR assay in nasal tissue from 19 dogs with idiopathic lymphoplasmacytic rhinitis. In that study, results were also negative for nasal tissue from 10 dogs with neoplasia and 10 dogs with aspergillosis. In another study,16 nasal signs were not recorded in medical records of 24 dogs seropositive for antibodies against B vinsonii subsp berkhoffii.
In contrast to findings of the present study, a previous study6 found that dogs seropositive for anti-Bartonella antibodies were 10 times as likely to have nasal discharge as were seronegative dogs, and nasal discharge has been mentioned in several case reports7–9 of dogs with bartonellosis. However, finding that dogs with bartonellosis can have nasal discharge does not necessarily indicate that dogs with nasal discharge are more likely to have bartonellosis.
It is possible that bartonellosis is more strongly associated with epistaxis and not other types of nasal discharge as a result of systemic vascular infection, secondary clotting disorders, or vascular proliferative lesions in the nasal cavity. In the present study, only 6 dogs had epistaxis alone, making it difficult for us to identify an association between bartonellosis and epistaxis. The first reported case of canine bartonellosis involved a dog with endocarditis and epistaxis,7 and a more recent report17 identified bartonellosis as a potential cause of epistaxis in 3 dogs, 2 of which were also seroreactive against other vectorborne pathogens. In a retrospective study18 of 35 dogs with epistaxis referred to a teaching hospital, 7 (20%) were found to have systemic disease, rather than primary nasal disease, and 2 of these dogs were seroreactive to both B vinsonii subsp berkhoffii and Ehrlichia canis and 1 of these dogs was seroreactive to B vinsonii subsp berkhoffii, although it also had nasal carcinoma. The potential or confirmed presence of concurrent infections and other diseases complicates attempts to elucidate the relationship between bartonellosis and epistaxis.
Future studies investigating potential relationships between specific diseases and infection with Bartonella spp would be enhanced through the use of improved testing methods. Two studies12,19 have failed to show a strong correlation between results of serologic and PCR assays used to detect Bartonella infection in dogs. Recent studies19–21 found that use of a modified insect cell culture–based growth medium (Bartonella D Proteobacteria growth medium) as a pre-enrichment step prior to the PCR assay resulted in improved detection of Bartonella DNA in dog and human blood samples.
EpiInfo, version 3.4.1, CDC, Atlanta, Ga.
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