Diagnostic Utility of Canine C-Reactive Protein, Haptoglobin, and 25-Hydroxyvitamin-D in Dogs with Nasal Cavity Disease

Abstract

In this prospective blinded study, canine C-reactive protein (c-CRP), haptoglobin (HPT), and 25-hydroxyvitamin-D (25(OH)D) were investigated for their diagnostic value in 55 dogs with nasal cavity disease (ND). After comprehensive diagnostics including a culture-dependent microbiological examination (ME) of nasal swabs, 17 dogs were excluded due to additionally detected systemic diseases or steroid pre-treatment. Included were 25 dogs with malignant ND (13 carcinomas and 12 sarcomas) and 30 dogs with benign ND (7 benign tumors, 13 idiopathic rhinitis (IR), and 10 others), as well as 10 controls. In none of the 72 dogs with ND was primary bacterial rhinitis diagnosed. Although within the reference interval, compared to the controls, c-CRP was significantly higher in dogs with ND in general and in every subgroup except for benign tumors. Serum HPT concentrations were not different among groups. Compared to the controls, 25(OH)D concentrations were significantly lower (p = 0.041) in malignant ND and sarcomas (p = 0.025). Despite pre-treatment with antibiotics (40/54; 74.1%), in 23/51 (45%) dogs, the ME was positive. Cultivated bacteria did not differ significantly between nasal diseases. The serum markers were not significantly different regarding the positivity of ME. In conclusion, the investigated serum markers were not clinically useful for the reliable detection of canine ND, as was the ME. Because of the low number of dogs with IR and positive or negative ME, further studies regarding c-CRP are needed in a larger group of IR dogs without concomitant diseases to reliably evaluate its utility in IR dogs with suspected secondary bacterial nasal infection.

Keywords: aspergillosis; idiopathic rhinitis; nasal discharge dog; nasal tumor; rhinoscopy.

Figure 1

Serum concentrations of c-CRP [mg/L] and 25(OH)D [nmol/L] in 55 dogs with nasal cavity disease and control group (CG). The gray marked area in all four boxplot diagrams shows the reference intervals of the respective parameter shown (c-CRP up to 15 mg/L, 25(OH)D 50–350 nmol/L). (A,B) Serum c-CRP was significantly increased in dogs with both benign (p = 0.006; B–ND) and malignant nasal cavity diseases (p = 0.002; M-ND) compared to the CG. This significant difference was due to significantly increased c-CRP levels in dogs with carcinomas (Cs) and idiopathic rhinitis (IR) but also in dogs with sarcomas (Ss) or other nasal diseases (Os), when compared to CG. Canine CRP values of dogs with benign tumors (BTs) were not significantly different from those in the CG. (C,D) Concentration of 25(OH)D was significantly decreased only in dogs with malignant neoplasia (M-ND) when compared to control animals (p = 0.041), with a particularly strong difference observed for dogs with sarcomas (p = 0.025). Data are shown in box and whisker plots. Upper and lower boxes represent the 25th and 75th percentiles (lower whiskers = minimum, upper whiskers = maximum values), respectively, and the line represents the median. The asterisks indicate the statistical significance with * = p ≤ 0.05, ** = p ≤ 0.01.

Figure 2

Results of culture-dependent microbiological examination (ME) in 51 dogs with nasal cavity diseases in contrast to the dogs of the control group (CG). (A) Despite pre-treatment with antimicrobials (AB), a positive culture-dependent ME was detected in 11/21 dogs (44%) with malignant nasal diseases (M-NDs; sarcomas and carcinomas; n = 25; 3 not performed and 1 only pre-reported negative) and 8/13 dogs (61.5%) with idiopathic rhinitis (IR). Only 1/7 dogs (14.3%) with a benign tumor (BT) had a positive ME, and only 3/10 dogs (30%) in the others group (in 2/3 dogs with Aspergillus spp. infections ME was negative). AB = antibiotic; BP = before presentation. In (A), the antibiotic pre-treatment is split into treatment less than 4 weeks before presentation (<4 weeks BP) and/or antibiotic treatment carried out before that time (>4 weeks BP). In one dog with carcinoma, no antibiotic history could be discovered. (B–D) Results of culture-dependent ME show non-significantly different cultivated bacteria. Graphs modified from Rösch et al., 2019 [2].

Figure 3

Serum c-CRP depending on positivity of culture-dependent microbiological examination (ME) in nasal cavity disease (ND) and depending on size of nasal tumors (T-categories according to Adams et al. [22]). (A) There were no significant differences between c-CRP concentrations in dogs with different nasal cavity diseases and positivity of culture-dependent ME (e.g., IR dogs: median c-CRP in positive ME 4.6 mg/L [IQR: 2.13–16.88] with highest values in dogs with lymphoplasmacytic inflammation/rhinitis and Pasteurella multocida and S. aureus; median c-CRP in negative ME 7.9 mg/L [IQR: 1.05–8.8]; malignant nasal disease (M-ND): median c-CRP in positive ME 4.5 mg/L [IQR: 3–10.3] with the highest value in Streptococcus canis; median c-CRP in negative ME 2.75 mg/L [IQR: 0.8–12.98]). (B) Canine CRP values in dogs with carcinomas, sarcomas, and benign tumors (BTs) with size of T1–T3 categories (6 carcinomas, 8 sarcomas, and 7 BT) are displayed versus dogs of T4 category with lysis of the cribriform plate (7 carcinomas and 3 sarcomas). There was no significant difference between c-CRP concentrations in different T-categories in dogs with different malignant tumors. (A,B) The dashed lines in both graphs indicate the upper reference interval of c-CRP at 15 mg/L.

Figure 4

Histopathological examination results in dogs with different kinds of rhinitis. (A) Rhinitis with different predominant inflammatory cells was detected. The main cell type communicated by the external laboratory was used for grouping as follows: lymphoplasmacytic, necrotizing, neutrophilic, plasmacytic, mycotic, and chronic rhinitis. The latter was defined as inflammatory lesions in combination with remodeling processes (fibrosis, bone remodeling, hyperplasia of the glands, or follicle formation). SNA = sinonasal aspergillosis. (B) Canine CRP (c-CRP) in correlation to different types of inflammation of nasal mucosa in dogs with idiopathic rhinitis is shown. The dashed line indicates the upper reference interval of c-CRP at 15 mg/L. In neutrophilic rhinitis, c-CRP values were not higher than in other types of rhinitis. Graph A modified from Rösch et al., 2019 [2].