Arsenic Trioxide-Induced Mandibular Osteomyelitis Associated with Mycotic Infestation: A Case Report

Abstract

Arsenic trioxide used in endodontic treatments has been shown to cause severe damages to surrounding bone and periodontal tissues. This report describes a case of alveolar osteomyelitis triggered by arsenic trioxide pulp devitalization and associated with mycotic infestation. Following clinical and radiological examinations, the concerned tooth was extracted, bone sequestrum was removed and granulation tissue was debrided. Histopathological biopsy examination, stained with hematoxylin/eosin, Grocott’s silver methenamine and periodic acid-Schiff, confirmed the diagnosis of chemical osteomyelitis associated with fungal infestation. Six months postoperatively, normal bone healing was observed.

Introduction

Arsenic trioxide (AT) is an inorganic compound generated by arsenic sulfide oxidation. In dentistry, Spooner suggested the use of AT to devitalize inflamed dental pulps when effective anesthesia was difficult to achieve [1]. However, studies have shown that the use of AT is unsafe because of its potential leakage into adjacent periosteum [2]. When in contact with hard/soft tissues, arsenic compounds have exhibited very toxic properties, causing severe damages to supporting bone and periodontal tissues such as osteomyelitis [3–5].

Osteomyelitis is an inflammatory bone process caused by infectious microorganisms [6]. It starts with soft tissue bacterial invasion which decreases the vascular supply of underlying bone causing ischemia and bone necrosis. Arsenical leakage is an uncommon etiology of osteomyelitis [1, 5, 7, 8].

This report describes a case of chemical alveolar bone osteomyelitis triggered by pulp devitalization with AT paste and associated with mycotic infestation.

Case Report

A 35-year-old patient suffering from unilateral, severe and continuous pain in the posterior right mandibular region was examined at the Oral Surgery Department, Saint Joseph University of Beirut. The patient indicated that pain was spontaneously initiated at a white-grayish patch situated in the lingual gingival area of the posterior right mandible, then progressively extended to the whole region, and only mildly ceased under the effect of analgesics. The patient had attended his general dental practitioner 1 year earlier with severe pain, and an endodontic treatment of the first inferior right molar was performed. When contacted, the treating dentist stated that after repetitive unsuccessful local anesthesia infiltrations, arsenical paste had to be applied to the pulp of tooth #46 in order to relieve the symptoms. The root canals were obturated during the same session, and the patient was not recalled for follow-up. Ten days after tooth devitalization, the patient noticed a white patch on the lingual side of the treated tooth along with tenderness and warmth in the infected area. He called his dentist who prescribed analgesics and anti-inflammatory drugs. However, the white patch continued to increase in size. Six months later, patient started experiencing pyrexia (38.5 °C), asthenia, and intermittent pain periods that lasted for hours. Medical and family history did not seem to have any relevance to the symptoms (ASA 1 patient). Clinical examination showed an extensive, crater-like, firm and irregular lesion of white-grayish color located in the lingual gingiva of tooth #46. Underlying alveolar bone was exposed and tooth #46 presented second degree mobility (Fig. 1a).

Fig. 1.

a Intra-oral situation at first clinical examination showing gingival recession and bone exposure on the lingual side of tooth #46. b Pre-operative periapical radiograph showing a severe horizontal bone loss crater (C) and a detached radio-opaque mass (S) facing first mandibular molar furcation

Periapical radiograph revealed incomplete endodontic treatment on tooth #46, severe vertical bone loss, periodontal ligament widening on both roots with a detached radio-opaque mass facing the furcation, similar in appearance to bone sequestrum (Fig. 1b).

Mandibular bone was diagnosed with aseptic chemical necrosis. Under local anesthesia (2.0% xylocaine), tooth #46 was extracted without flap elevation. Residual bone sequestrum, measuring approximately 1.2 × 0.8 cm, was also removed along with surrounding hard and soft necrotic tissues. Alveolar defect granulation tissue was meticulously debrided to provoke active bleeding. No grafting material was inserted into the residual defect. Specimen was sent for histological examination. Postoperatively, the patient was prescribed Augmentin 1 g oral (amoxicillin 875 mg/clavulanic acid 125 mg) twice a day for 7 days and 0.12% chlorhexidine mouth rinsing solution twice a day for 10 days.

Histopathological microscopic examination of the preparation with hematoxylin/eosin staining showed several empty bone lacunae denoting necrotic bone marrow residue (Fig. 2a). Grocott’s silver methenamine and periodic acid-Schiff revealed non-parallel, septate fungal filament and spore infiltration of necrotic bone and surrounding fibrous connective tissue (Fig. 2b, c). Diagnosis of chemical osteomyelitis associated with fungal infestation was confirmed.

Fig. 2.

a Histopathological examination after hematoxylin and eosin (H&E) coloration showing empty bone lacunae denoting necrotic bone marrow residue. b Histopathological examination after Grocott’s silver methenamine (GSM) coloration showing fungal filaments infiltrating fibrous connective tissue and necrotic bone. c Histopathological examination after periodic acid-Schiff (PAS) coloration showing wide, non-parallel septate fungal filaments

Ten days postoperatively, all major symptoms had ceased and no signs of inflammation were observed. Even though histopathology results clearly indicated fungal infestation, postoperative clinical examination of the surgical site showed adequate primary healing and no additional anti-fungal medication was prescribed. 6 months post-op, retro-alveolar radiograph showed normal bone healing (Fig. 3a, b).

Fig. 3.

a Surgical site 10 days after the sequestrectomy. b 6 months postoperative radiograph

Discussion

Diffusion of AT to the periodontal tissues may cause periodontal tissue necrosis, extensive bone necrosis in the mandibular ramus [3] and the maxilla [9], oroantral fistulas [5], and irreversible lower lip paresthesia [8]. In this case, the use of AT for pulp devitalization caused extensive chemical alveolar osteomyelitis.

Histological analysis showed necrotic bone infiltrated by fungal filaments. This may be due to the association of exposed necrotic bone with poor oral hygiene for an extended time interval (1 year). No cases of alveolar osteomyelitis associated with mycotic infestation were described in the literature.

In a case of limited necrosis, Chen et al. proposed complete elimination of the arsenical paste through intracanal irrigation with physiological saline to preserve the concerned tooth and remove the sequestrum only [1]. N. Özmeriç effectuated a successful amputation of involved root followed by osteoplasty to adjust the osseous contour [7]. Garip et al. used an autogenous graft to compensate an extensive sequestrectomy. However, grafting increased the risk of postoperative complications [9]. Lu et al. used adjunctive hyperbaric oxygen therapy for a case of AT osteomyelitis to induce neo-vascularization of the ischemic structures [8].

In the present case, mobility, severe destruction of mandibular lingual bone and furcation involvement of tooth #46 imposed its extraction along with sequestrectomy of arsenic-induced necrotic bone. Normal healing was obtained even though no grafting materials nor adjuvant therapy were applied. This may be due to the contained intra-bony defect morphology, and the meticulous debridement of the concerned site that induced active bleeding.

AT is a toxic agent that may lead to local or extensive alveolar necrosis and fungal infection. With all these pathogenic risks, the use of arsenic trioxide in modern dentistry should be discarded.

Authors’ Contributions

SM contributed to data curation and writing—original draft preparation. AM contributed to writing—reviewing and editing. CM contributed to conceptualization and validation. JB contributed to conceptualization, methodology, supervision, and validation.

Funding

No funding was received to assist with the preparation of this manuscript.

Code Availability

Not applicable.

Declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Due to the retrospective nature of this report, Ethical approval was waived by the local Ethics Committee of the Saint Joseph University of Beirut.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Consent for Publication

The participant has consented to the submission of the case report to the journal.