Original Article

Association of Actinomyces with Allergic Rhinitis, Adenotonsillar Hypertrophy and Chronic Recurrent Tonsillitis and Its Histopathological Findings

10.4274/nkmj.galenos.2020.784937

  • İlke Evrim SEÇİNTİ

Received Date: 24.08.2020 Accepted Date: 22.12.2020 Nam Kem Med J 2021;9(1):13-17

Aim:

To evaluate the prevalence of adenotonsillar Actinomyces with histopathological findings and to determine the relationship of Actinomyces with allergic rhinitis (AR), adenotonsillar hypertrophy (ATH) and chronic recurrent tonsillitis (CRT).

Materials and Methods:

Histopathological sections were retrospectively analyzed in 228 patients who underwent adenoidectomy, bilateral tonsillectomy, and adenotonsillectomy. The presence of Actinomyces, cryptitis, and severity of inflammation were determined. Data were analyzed with the Statistical Package for the Social v.21.0 package software. The statistical significance level was accepted as p<0.05.

Results:

Actinomyces was detected in 39 (17.1%) patients. Actinomyces was seen at a similar rate in ATH and CRT (p=0.08) (14.6% and 24.6%, respectively). The diameter of the tonsils with Actinomyces were larger than those without Actinomyces (p<0.01). The frequency of cryptitis in tonsils with Actinomyces histopathologically (p=0.03) and the degree of inflammation in the surface epithelium (p<0.01) were increased. Actinomyces was found more frequently in patients with AR than in patients without AR (p=0.02) (25.7% and 13%, respectively).

Conclusion:

Our study shows that adenotonsillar Actinomyces colonization may cause ATH, CRT and AR, and AR may be one of the factors in the etiology of ATH.

Keywords: Actinomyces, adenotonsillar hypertrophy, allergic rhinitis, recurrent tonsillitis

INTRODUCTION

Palatine, tubal, pharyngeal (adenoid) and lingual tonsils form Waldeyer ring, which is an important lymphatic structure of the upper airway1. Adenoidectomy and tonsillectomy are the most common surgical procedures in both pediatric and adult patients. The most common indications for surgery are adenotonsillar hypertrophy (ATH) and chronic recurrent tonsillitis (CRT), which may cause obstructive sleep-related breathing disorders2,3. Although the causes of ATH are still unclear, there are studies in the literature showing that allergy may be a risk factor4.

Actinomyces are Gram-positive, anaerobic, immobile, filamentous and rod-shaped commensal bacteria in the normal flora of the oropharyngeal, genitourinary and gastrointestinal tract5. They can resemble fungi because of their filamentous structure. In the literature, the incidence of Actinomyces in tonsil and adenoid has been reported in very variable rates, ranging from 0.3% to 40.7%2,5-9. There are different opinions on the role of Actinomyces in the etiology of tonsil/adenoid hypertrophy and CRT. In addition to the studies suggesting that Actinomyces plays a role as an etiologic agent in these pathologies7,9-12, there are also studies suggesting that it is only a saprophyte agent13. However, few studies have examined the histopathological effects of Actinomyces on tonsil and adenoid tissues14,15. Allergic rhinitis (AR) is an inflammatory disease caused by IgE-mediated type 1 hypersensitivity reaction. AR has many factors in etiopathogenesis, including various fungi16. To date, no studies have investigated the relationship between AR and the presence of adenotonsillar Actinomyces in the literature. However, it is known that Actinomyces plays a role in the etiology of hypersensitivity pneumonia (extrinsic allergic alveolitis)17.

This study aims to determine the prevalence of Actinomyces in adenoidectomy, tonsillectomy and adenotonsillectomy materials, to investigate the relationship of Actinomyces with AR, ATH and CRT, and to discuss all findings in the light of literature. This is the first study in the literature to investigate the relationship between AR and adenotonsillar Actinomyces.


MATERIALS AND METHODS

Patient Selection

This retrospective study included 228 patients who underwent adenoidectomy (n=143), bilateral tonsillectomy (n=29), and adenotonsillectomy (n=56) at Silifke State Hospital between January 2013 and December 2015. The study were approved by the Hatay Mustafa Kemal University of Local Ethics Committee (protocol number: 10, date: 16.01.2020). Unilateral tonsillectomies were excluded because of different surgery indications. Data on age, sex, diagnosis of AR, indications for operation, the largest diameters of tonsils and adenoids were obtained from the patient files and pathology reports.

Histopathological Evaluation

Hematoxylin-eosin stained histopathological sections of a total of 369 tissue materials taken from 228 patients were re-evaluated on the Olympus BX53 (Olympus, Tokyo, Japan) light microscope and photographed with the Olympus DP20 digital imaging system (Olympus, Tokyo, Japan). Tonsillar Actinomycosis diagnosis is made either by the presence of sulfur granules in the form of a basophilic mass with a granular center and the radial fringes around it or by the presence of a unique Actinomyces filament in the tonsillar tissue and/or crypt15 (Figure 1).

The presence of Actinomyces, cryptitis (evaluated only in palatine tonsils because there was no crypt in adenoid tissue), inflammation in the surface epithelium and lymphoid hyperplasia were re-evaluated. Inflammation in the surface epithelium was scored semiquantitatively as 0: none, 1: mild, 2: moderate, and 3: severe. Lymphoid hyperplasia was classified as follicular hyperplasia, paracortical hyperplasia and mixed hyperplasia (follicular + paracortical).

Statistical Analysis

All clinical, histopathological and demographic data obtained from this study were analyzed with Statistical Package for the Social (SPSS) v.21.0 software package program (SPSS Inc, Armonk, NY, US). The Pearson chi-square test was used for the analysis of qualitative data. For quantitative data that were not normally distributed were statistically analyzed with the Kolmogorov-Smirnov and the Mann-Whitney U tests. Correlation analyses were performed with the Spearsman’s rank correlation test. Statistical significance was accepted as p<0.05 in all analyses.


RESULTS

The median age of all patients (n=228) was 8±5.06 years (minimum: 4, maximum: 39). 132 of them were male (57.9%) and 96 were female (42.1%). Actinomyces was detected in 39 patients (17.1%). Actinomyces was seen in 29 (34.1%) of 85 patients with tonsillectomy when adenoidectomy was excluded. The incidence of Actinomyces was similar in both sexes (p=0.20). The median age of the patients with Actinomyces was higher than that of those without Actinomyces (p<0.01). The median age of the patients with Actinomyces was 11±7.8 years and the median age of the patients without Actinomyces was 8±3.6 years. Actinomyces was seen in 25 (14.6%) of 171 patients who underwent surgery for ATH and in 14 (24.6%) of 57 patients who had surgery for CRT, and no significant difference was observed (p=0.08). The diameters of the tonsils (palatine + pharyngeal) with Actinomyces were larger than those without Actinomyces (p<0.01). Histopathologically, cryptitis was observed more frequently in tonsils with Actinomyces (p=0.03) and the degree of inflammation in the surface epithelium was increased (p<0.01). There was no difference in lymphoid hyperplasia types (p=0.45). Follicular hyperplasia was high in both groups. Comparison of the presence of Actinomyces with other data and statistical test results are summarized in Table 1. Actinomyces was localized only in the right tonsil in 11 (28.8%) of 39 patients with Actinomyces. Other localizations of Actinomyces are shown in Table 2.

Actinomyces was observed in 19 (25.7%) of 74 patients with AR, while 20 (13%) of 154 patients without AR had Actinomyces, and the difference was statistically significant (p=0.02). The diagnosis of AR was higher in patients operated for ATH than in patients operated for CRT (p=0.013). Adenoid diameters of patients with AR were larger than those without AR (p=0.046).


DISCUSSION

Actinomyces spp. are found in normal flora of the oropharyngeal, genitourinary and gastrointestinal tract5. Histopathological examination is more valuable than microbiological culture in the diagnosis of Actinomyces18. There is a wide range in the literature regarding the frequency of tonsillar Actinomycosis ranging from 0.3% to 40.7%. We wanted to investigate the incidence of Actinomyces in our series. Coban et al.2 found only 3 (0.3%) Actinomyces in 1,078 tonsillectomy cases. Riffat and Walker6 found 221 (18.2%) Actinomyces of 1,213 tonsillectomy cases. Ashraf et al.5 found 83 (40.7%) Actinomyces of 204 tonsillectomy cases. We found Actinomyces at the rate of 17.1% (n=36) in our series. Since Actinomyces is found as saprophyte in oral flora, the general opinion is that it is also found as saprophyte in tonsils. Therefore, there may be different attitudes among pathologists to specify tonsillar Actinomyces in the report and this may lead to differences in the results of retrospective studies using the archive of reports. In fact, if only pathology reports were taken as the basis in our study, Actinomyces was reported in 11 (4.8%) of 228 patients, but when preparations were re-evaluated, the number of patients with Actinomyces was revised to 39 (17.1%). In some studies, it was reported that tonsillar Actinomycosis was seen more frequently in adults than in children5,11,12,19,20, particularly in older children5,21. Some studies have shown that Actinomycosis is not age-related15,22. In this study, the median age value (median age: 11) of those with Actinomyces colony was greater than that of those without Actinomyces (median age: 8 years) (p<0.01).

In most of the studies in the literature, the rate of tonsillar Actinomycosis was found to be similar in both sexes5,15,21,22. Similar findings were obtained in this study, which is consistent with the literature.

The role of Actinomyces in the etiology of ATH and CRT remains unclear. In addition to the studies suggesting that Actinomyces has a role in the etiology of hypertrophy and recurrent tonsillitis7,10-12,23, there are also studies suggesting that it is not associated with these diseases5,11,13,24. In the study of Kutluhan et al.15, Actinomyces was found in 33.3% of tonsils and it was revealed that Actinomyces was more common in tonsillar hypertrophy (61.5%) than in recurrent tonsillitis (21.9%). Besides, they found that the volume of tonsils found in Actinomyces was larger than in those without Actinomyces. Similarly, Daneshmandan et al.22 found that tonsil volumes with Actinomyces (mean 8.65 mL) were larger than in those without Actinomyces (mean 4.48 mL). In contrast to these studies, Jones et al.25 found a negative correlation between tonsillar Actinomyces colonization and hypertrophy and found a higher rate of Actinomyces in patients with recurrent tonsillitis compared to hypertrophy patients. Toh et al.11 reported that Actinomyces did not affect the tonsillar size. In this study, a similar rate of actinomyces was detected in patients operated for hypertrophy and recurrent tonsillitis (p=0.08). The diameters of the tonsils (palatine and pharyngeal tonsils) with Actinomyces were larger than in those without Actinomyces (p<0.01), suggesting that Actinomyces plays a role in the etiology of ATH. Tonsils with Actinomyces showed more cryptitis (p=0.03) and inflammation in the surface epithelium was more severe (p<0.01). This suggests that Actinomyces may be an effective pathogen in the etiology of recurrent tonsillitis.

AR is one of the most common chronic diseases in children26. Few studies have investigated the relationship between AR and AH and there is no consensus between these studies. Sadeghi-Shabestari et al.27 found a significant correlation between positive skin prick test and high serum IgE levels with ATH. Modrzynski and Zawisza28 also reported that AR might cause AH. Similarly, Bozkurt et al.29 found that adenoid volumes of patients with AR were higher than those of patients without AR. In contrast to these studies argueing that AR causes AH or exacerbates existing AH, Ameli et al.30 found that patients with AR had smaller adenoid volumes than those without AR, suggesting that anterior nasal obstruction stopped adenoid growth. In our study, the adenoid size was higher in patients with AR (p=0.046) and there was a positive correlation between them (p=0.04). Our findings support the view that AR may cause or increase existing AH, as in the studies of Sadeghi-Shabestari et al.27 and Modrzynski and Zawisza28. Some fungi have been reported to play a role in the etiology of AR in the literature. In their study, Namyslowski et al.16 found Candida albicans in 3.8%, Aspergillus fumigatus in 11.5%, Alternaria alternata in 3.8%, Mucor racemosus in 7.6% and Cladosporum herbarum in 7.6% in patients with AR. Actinomyces is also known to be similar to fungi because of their filamentous structure, and Actinomyces like Aspergillus have been shown to act as active pathogens in allergic diseases such as hypersensitivity pneumonia17. In our study, Actinomyces was found to be more frequent in patients with AR (25.7% and 13%, respectively) than in those without AR, and there was a positive correlation between them (p=0.02).

Study Limitations

Our study’s retrospective design and therefore, the lack of access to drug history and laboratory values of all patients constitute the limitations of our study.


CONCLUSION

ATH and recurrent tonsillitis, which can cause obstructive sleep-related respiratory disorders, are the most common diseases and adenotonsillectomy is one of the most common surgical procedures in the treatment of these diseases. However, the etiologic cause of ATH is still unclear. Our study shows that adenotonsillar Actinomyces colonization may cause ATH, recurrent tonsillitis, and AR. It also suggests that AR may be involved in the etiology of ATH. Establishing causal relationships will contribute to the development of both preventive and therapeutic approaches. Our study is the first study to investigate the relationship between AR and Actinomyces.

Ethics

Ethics Committee Approval: The study were approved by the Hatay Mustafa Kemal University of Local Ethics Committee (protocol number: 10, date: 16.01.2020).

Informed Consent: Consent form was filled out by all participants.

Peer-review: Externally peer-reviewed.

Financial Disclosure: The author declared that this study received no financial support.


Images

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