Eosinophilic and Mixed‐Cell Infiltration in Odontogenic Cutaneous Sinus Tracts of a Dog

ABSTRACT

A 7‐year‐old neutered female Shih Tzu presented with bilateral skin lesions and a subcutaneous mass in the submandibular region. The initial lesion on the right appeared as a plaque, followed by the development of an ulcer on the opposite side 2–3 days later. Despite treatment with antibiotics, antifungal drugs and anti‐inflammatory steroids, lesions persisted. There was an initial improvement with steroids; however, the lesions developed into scars, erythema and papules. A biopsy revealed eosinophilic and mixed‐cell dermatitis requiring treatment with immunosuppressive steroids and cyclosporine, which resolved the plaque and ulcer but only partially reduced the subcutaneous mass. Surgical resection was considered, and subsequent skull radiography revealed alveolar bone loss. During surgery, a sinus tract was identified extending from teeth 309 to 409, indicating that the tissue changes were likely due to drainage from the periodontal disease. Based on clinical history and examination results, the case was definitively diagnosed as an odontogenic cutaneous sinus tract (OCST). Following surgery, no recurrence of the lesion or mass was observed. This is the first case report describing the histopathological features of a submandibular OCST in a dog, highlighting the importance of considering this condition when submandibular lesions do not fully respond to immunosuppressive therapy.

A 7‐year‐old spayed female Shih Tzu with bilateral submandibular lesions and a subcutaneous mass showed partial response to immunosuppressive therapy but failed to heal completely. Radiography revealed alveolar bone loss, and surgery confirmed an odontogenic cutaneous sinus tract (OCST). Complete resolution after sinus tract excision and tooth extraction emphasizes the need to consider OCST in persistent submandibular lesions unresponsive to immunosuppressive therapy.

1. Introduction

Odontogenic cutaneous sinus tracts (OCST) are rare in humans and can easily be misdiagnosed as non‐odontogenic lesions (Johnson et al. 1999). A cutaneous lesion on the head or neck may be remote from the original site of the odontogenic disease, leading to frequent misdiagnosis and improper treatment of a chronically draining cutaneous sinus tract. Misdiagnosis as a simple skin problem can lead to unnecessary prescription of antibiotics, surgical removal and biopsy, delaying proper diagnosis (Curvers et al. 2017). The most common cause of OCST in humans is chronic periodontal disease, and it can also be caused by pulp infection, root fracture, chemical irritation, chronic apical periodontitis, or dental trauma (Gupta et al. 2011). OCST is most frequently located in the mandibular region and its most common anatomical shape is that of a nodule (Guevara‐Gutiérrez et al. 2015). In veterinary medicine, OCST is rarely reported, and there have been no cases of bilateral lesions (Yang et al. 2019). Furthermore, only a few studies have histologically examined the dental pulp tissue or sinus tract in human medicine (Lee and Yun 2017). Moreover, no previous studies have histologically investigated the sinus tract in veterinary medicine.

This report describes bilateral OCST in a dog with eosinophilic cutaneous lesions. Histopathological and macroscopic examination of the skin lesion revealed ulcerative and mixed‐cell dermatitis, whereas the analysis of the sinus tract identified a granuloma. To our knowledge, this is the first case report detailing the histopathology of OCST in a dog.

2. Case Description

A 7‐year‐old spayed female Shih Tzu presented with bilateral cutaneous lesions and a subcutaneous mass in the submandibular region (Figure 1A,B). The lesion on the right side developed 2 weeks before the visit, and the left lesion occurred 2–3 days after the onset of the right lesion. The right submandibular lesion (Figure 1A) started with erythema and was identified as a plaque at the initial visit, whereas the left submandibular lesion was identified as an ulcer (Figure 1B). Two weeks prior to the first visit, antibiotics were administered at a local animal hospital; however, there was no response to treatment. At the first visit, cytology, bacterial and fungal cultures, a skin scraping test and Wood's lamp test were performed, with no remarkable findings. A punch biopsy was performed at the same site. Histopathological and cytological analyses revealed no evidence of parasitic infection or autoimmune disease, such as free‐floating acantholytic keratinocytes and non‐degenerative neutrophils. Histopathological examination of the biopsy specimens revealed a focal erosion of the epidermis with mixed inflammation and reactive fibroplasia in the dermis. The inflammatory infiltrate predominantly comprised eosinophils, with scattered macrophages and mast cells. In deeper layers, eosinophils, lymphocytes and plasma cells were observed in perivascular locations within the reactive fibroplasia (Figure 2A,B). Additional Gomori methenamine silver and periodic acid–Schiff staining yielded negative results. Therefore, fungal infection could not be confirmed. On the basis of these findings, a tentative diagnosis of eosinophilic and mixed‐cell dermatitis was made.

FIGURE 1.

Changes of bilateral cutaneous lesions in the submandibular area. (A) A plaque in the right submandibular region accompanied by a subcutaneous mass, (B) an ulcer in the left submandibular region at the initial visit. After 35 days of immunosuppressive treatment, cutaneous lesions of the left (C) and right (D) were diminished; however, the subcutaneous masses persisted.

FIGURE 2.

Histopathology of tissue from the right submandibular lesion (A and B) and the extracted sinus tract (C and D). (A) The biopsy revealed ulceration and exfoliation of the epidermis, along with crust formation (arrows), interface dermatitis at the epidermal–dermal junction and inflammatory cell infiltration around the skin appendages. (B) The infiltrating inflammatory cells were predominantly eosinophils with scattered macrophages and mast cells with the additional presence of lymphocytes and plasma cells. (C) The extracted sinus tract showed inflammatory cell infiltration and the presence of granuloma. (D) Mature fibrous connective tissue mixed with inflammatory cells, mainly histiocytes, lymphocytes and plasma cells, along with thickened oedematous collagen, was noted. All sections were stained with haematoxylin and eosin. Scale bars: 100 µm (A), 50 µm (B), 800 µm (C), 50 µm (D).

Following the biopsy, prednisolone (0.5 mg/kg orally (PO) q12h; Yuhan, Seoul, South Korea), amoxicillin–clavulanic acid (25 mg/kg PO q12h; Kuhnil, Seoul, South Korea), famotidine (0.5 mg/kg PO q12h; Nelson, Eumseong, South Korea) and tramadol (3 mg/kg PO q12h; Yuhan, Seoul, South Korea) were prescribed to manage pain, infection or inflammation. Afoxolaner (18.75 mg/body PO once a month; Merial Saúde, Paulinia, SP, Brazil) was prescribed to eliminate ectoparasites. Initial signs of healing were evident after administering an anti‐inflammatory dose of glucocorticoids; the ulcer and plaque resolved, and the cutaneous lesions evolved into scars, erythema and papules. Prednisolone was tapered to 0.5 mg/kg, q24h for 2 weeks, but the lesions recurred as erosions during tapering, suggesting that the treatment period was insufficient. Consequently, the prednisolone dosage was increased to 1 mg/kg q12h. After 3 weeks, elevated liver enzyme levels were detected, likely an adverse effect of prednisolone. Prednisolone was tapered again to 0.5 mg/kg q24h, and cyclosporin (5 mg/kg PO q24h; Chong Kun Dang, Seoul, South Korea) and hydrocortisone ointment (1% q24h; Vivozon, Hwaseong, South Korea) were added to the treatment regimen. Following these adjustments, the ulcer, plaque and other skin lesions resolved; however, the subcutaneous mass persisted (Figure 1C,D).

After 63 days of immunomodulatory therapy, no further improvement was observed, prompting additional examinations. Skull radiography revealed alveolar bone loss around teeth 309 and 409 (Figure 3A,B), leading to the inclusion of OCST in the differential diagnosis. Surgical resection was performed to remove the submandibular mass, during which OCST was definitively diagnosed by identifying the sinus tract extending from the inside of the mouth to the skin. The sinus tract was subsequently excised (Figure 4). The skin wounds healed completely within 4 weeks post‐surgery. Twenty‐five days after surgery, dental scaling was performed, and teeth 309 and 409 were extracted. At the follow‐up examination 2 weeks later, the dog's ability to eat dry food had returned, and no recurrence of the lesion was observed for the remainder of its life (up to 1139 days after surgery). Histological analysis of the tissue extracted from the sinus tract revealed collagenous, fibroadipose and inflammatory tissues (Figure 2C,D).

FIGURE 3.

Skull radiographs before surgery showing alveolar bone loss (indicated by round circles) around tooth 409 (A) and tooth 309 (B), along with irregularities in the tooth roots: (A) right lateral view; (B) left lateral view.

FIGURE 4.

Sinus tracts identified during surgery in the left submandibular area (A and B) and the right submandibular area (C and D).

3. Discussion

OCST is an uncommon condition where the cutaneous lesion is often distant from the infection site, making diagnosis challenging (Sato et al. 2015). The clinical signs are nonspecific and ambiguous, with skin lesions being the primary presentation in most cases, necessitating multiple dermatological tests (Al‐Obaida and Al‐Madi 2019). Periodontal disease is frequently overlooked due to the absence of clear dental symptoms, leading to it not being initially recognized as a dental issue (Sammut et al. 2013). In human medicine, OCST is often diagnosed only after a prolonged period, during which unnecessary antibiotic treatments and surgeries are sometimes suggested or performed (Vidémont et al. 2012). To ensure an accurate diagnosis, a thorough intraoral examination and additional radiographic imaging are recommended (Yang et al. 2019).

In a large human study, OCST prevalence was found to be 14.7% among 728 endodontically treated teeth (Samir et al. 2011). In dogs, severe periodontal disease can lead to complications such as tooth loss, oral‐nasal fistula, peri‐endo abscess, fractures, ocular infection, chronic osteomyelitis and even oral cancer (Niemiec 2008). However, the frequency and aetiology of OCST in dogs remain unclear, with only one case reported to date (Yang et al. 2019). This is likely due to ambiguous clinical signs, as dogs often tolerate dental discomfort without exhibiting a clear pain response, causing owners to overlook dental issues. Therefore, when skin lesions, particularly in the submandibular region, do not respond adequately to treatment, additional tests such as radiography, ultrasound, computed tomography and magnetic resonance imaging should be considered, even if a dental examination does not reveal signs of OCST (Mauldin 2019). As in previous cases, this dog showed no obvious clinical signs of dental disease (Yang et al. 2019).

The differential diagnosis for a mass in the cervical region can include conditions such as lymphadenopathy, foreign bodies, abscess and tumours like thyroid carcinoma and lymphoma (Adachi et al. 2015; Johnson et al. 1999; Sato et al. 2015). In the present case, histopathology ultimately ruled out the presence of a tumour. To differentiate OCST, it is crucial to exclude neoplasia, making biopsy an essential tool when a tumour is suspected (Czock et al. 2005). Unlike previously reported cases, the mass in this case was confirmed to be bilateral (Yang et al. 2019). Therefore, depending on the location of periodontal disease, bilateral OCST may be present. Furthermore, OCST should be considered one of the differential diagnoses for cervical masses.

In dogs, eosinophilic lesions are usually associated with autoimmune diseases or parasitic infections and can also result from acute eosinophilic dermatitis with oedema (Bloom 2006). Cytological and histopathological analyses indicated the absence of non‐degenerate neutrophils and free‐floating acantholytic keratinocytes, thus reducing the likelihood of autoimmune disease. Moreover, these analyses, along with the skin scraping test, found no evidence of parasitic infection, which was confirmed to be absent when an insufficient therapeutic response to antiparasitic treatment was observed. Eventually, the eosinophilic and mixed‐cell dermatitis observed in the skin was considered a response to OCST. Previous studies in dogs have shown that eosinophil infiltration can occur in the stratum corneum during recovery after acute skin barrier disruption (Vidémont et al. 2012). Thus, the eosinophilic skin lesions in this case were likely a result of the skin's healing process in response to inflammation caused by OCST.

Histopathological findings of OCST in human medicine are often described as nonspecific inflammatory lesions and chronic inflammation in the pulp tissue (Bloom 2006; Nakamura et al. 1999), with some cases presenting as a pyogenic granuloma (Lee and Yun 2017). In this case, histopathological examination of the sinus tract revealed granulomatous inflammation. Granulomas typically form in response to persistent irritants that the body cannot eliminate, such as infections or a degenerated extracellular matrix in the skin (Guevara‐Gutiérrez et al. 2015). The extracellular matrix degeneration may result from periodontal inflammation, and the loss of alveolar bone could also contribute to this process (Nakamura et al. 1999). Immune suppression treatments, including prednisolone and cyclosporine, partially alleviate the symptoms by suppressing the cytokines involved in granuloma formation (Eyerich and Eyerich 2018). Consequently, immunosuppressive therapy was partially effective in resolving cutaneous lesions.

To effectively treat OCST and prevent recurrence, it is crucial to adequately address periodontitis, including extracting inflamed teeth (Sammut et al. 2013). In human medicine, non‐surgical treatments, such as root canal therapy, have been successful (Lee et al. 2019). However, this approach is less common in dogs, where periodontal therapy is primarily achieved through tooth extraction or the removal of subgingival plaque and calculus scaling (Niemiec 2008). Unlike many cases in human medicine where recurrence occurs after only skin lesion removal, this dog received comprehensive treatment for periodontal disease through tooth extraction and scaling. No recurrence was observed, similar to the outcomes reported in previous studies (Al‐Obaida and Al‐Madi 2019). Therefore, OCST caused by periodontitis can effectively be managed through periodontal treatments, including tooth extraction and scaling.

4. Conclusion

This case highlights that bilateral masses with cutaneous skin lesions may be due to OCST, and that immunosuppressive drugs can serve as an effective adjunctive treatment. It also showed that OCST can manifest as granulomatous lesions resulting from chronic inflammation associated with periodontal disease. Furthermore, OCST can be misdiagnosed as an eosinophilic skin disease, as both conditions may respond to immunosuppressive treatments. Therefore, when skin lesions, particularly in the submandibular region, do not adequately respond to immunosuppressant therapy, OCST may be considered a potential underlying condition, and further differential diagnoses should be explored.

Author Contributions

Sungjae Lee: conceptualization, formal analysis, writing – original draft. Jooyoung Park: conceptualization, formal analysis, writing – original draft. Yeon Chae: formal analysis, writing, review, editing. Hakhyun Kim: supervision. Taesik Yun: supervision. Byeong‐Teck Kang: conceptualization, writing – review and editing, supervision.

Ethics Statement

The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a case report with no original research data.

Consent

The owner consented to the disclosure of this case.

Conflicts of Interest

The authors declare no conflicts of interest.

Peer Review

The peer review history for this article is available at https://publons.com/publon/10.1002/vms3.70327

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.