Effect of imatinib on oral wound healing after extraction

These ADRs typically range from mild to moderate, but excessive toxicity can occur, especially at higher doses, resulting in dose interruptions, dose reductions, and sometimes treatment discontinuation.

Imatinib is also associated with various cutaneous adverse effects (for example, photosensitivity, Stevens-Johnson syndrome, psoriasis, acute neutrophilic dermatosis)

and is not devoid of oral adverse effects.

Oral lichenoid reactions,

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blue-gray asymptomatic hyperpigmentation of the hard palate,

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oral melanosis,

stomatitis,

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and taste disturbances

have all been reported. Imatinib can also disturb bone and mineral homeostasis, which is putatively a mechanism by means of which it causes osteonecrosis of the jaw.

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Case Report

We report the case of a 58-year-old man who sought treatment in December 2020 at a prosthodontic clinic with a dislodged crown and core buildup and multiple recementations of tooth no. 19. The patient had a medical history of a gastrointestinal stromal tumor, which was surgically removed in 2019. He received no chemotherapy or radiation therapy afterward, but his oncologist prescribed 400 mg of imatinib orally daily. He was compliant with drug therapy for 16 months at the day he came to the dental clinic. No other medications or systemic conditions were noted.

Tooth no. 19 was treated endodontically, and the mesial root was ankylosed. The crown of tooth no. 19 had been dislodged several times. The patient consented to have the crown removed to determine restorability. The entire crown with core and cement were dislodged easily with no dentine ferrule. These findings were explained to the patient and a discussion of treatment options followed, including crown lengthening, post and core, and crown; implant; removable partial denture or overdenture; and no treatment. The advantages and disadvantages of each option were discussed at length. The patient consented for extraction of tooth no. 19, ridge preservation, and future implant placement.

Tooth no. 19 was surgically extracted in December 2020. The procedure included local anesthetic (mandibular nerve block and local infiltration) administered as 2% lidocaine with 1:100,000 epinephrine, intrasulcular incision at tooth no. 19, raised limited extent full-thickness flaps, and extraction of tooth no. 19 using Piezotome (Acteon), elevator, and forceps. The socket was curetted and irrigated with sterile water. The ridge was preserved with particulate allogenic bone graft (a mixture of mineralized and demineralized cortical bone; LifeNet Health), and the bone graft was covered with a Cytoplast (Osteogenics Biomedical) membrane. The flaps were sutured with 4.0 Cytoplast polytetrafluoroethylene sutures (Osteogenics Biomedical). Postoperative instructions were given, along with a prescription for 875 mg of amoxicillin and clavulanic acid (Augmentin; GlaxoSmithKline) orally twice per day and 15 mL of chlorhexidine mouthrinse to be used gently for 30 seconds twice per day. For pain, the patient was instructed to take 600 mg of ibuprofen every 6 hours as needed.

At the 1-week postoperative appointment, the patient reported no pain during the initial few days after surgery. However, he stopped taking amoxicillin and clavulanic acid 3 days after the surgery because he could not tolerate it due to severe diarrhea. He started feeling dull pain at tooth no. 19 after stopping antibiotic therapy. Intraoral examination revealed that the surgical site had no exudate and all sutures and the membrane were in place. However, soft tissue at the tooth no. 19 site was red and painful during palpation. The patient was prescribed a course of 500 mg of amoxicillin orally 3 times per day, which he tolerated well. After taking amoxicillin for 3 days, the patient began experiencing the same degree of dull pain at the surgical site and reported a “decay” taste. Intraoral examination revealed findings similar to those at the 7-day postoperative examination. To exclude the possibility of soft-tissue irritation from the Cytoplast membrane, the sutures and membrane were removed 10 days after extraction and ridge preservation. No exudate was observed from the bone graft within the socket. The bone graft was irrigated once with chlorhexidine and then multiple times with sterile water. A BioXclude (Snoasis Medical) membrane was placed to cover the bone graft, and the soft tissue was then sutured with 4.0 Cytoplast polytetrafluoroethylene sutures.

Revision surgery of ridge preservation at tooth no. 19 site was performed 8 weeks after extraction owing to loss of the coronal portion of the bone graft. After local anesthesia with 2% lidocaine with 1:100,000 epinephrine, a midridge incision at tooth no. 18 through tooth no. 19 and an intrasulcular incision at tooth no. 20 were made, full-thickness flaps were reflected, and the ridge height at tooth no. 19 was enhanced with a mixture of mineralized and demineralized cortical bone particulates and a DynaMatrix membrane (Keystone Dental Group), followed by reposition of the flaps and suture with 5.0 Cytoplast polytetrafluoroethylene sutures. Primary closure was achieved. The patient was prescribed another course of 500 mg of amoxicillin orally 3 times per day and 15 mL chlorhexidine mouthrinse to be used gently for 30 seconds twice per day. For pain, the patient was instructed to take 600 mg of ibuprofen every 6 hours as needed.

The patient reported no pain at the surgical site during the 1-week postoperative examination. However, the membrane was exposed. Intraoral examination revealed that the soft tissue at the surgical site was reddish, especially at the buccal side (Figure 2A). The redundant fragments of the membrane were cut off, leaving the remaining membrane intact because it still covered the bone graft and was held in place with sutures. At the 2-week postoperative examination, the soft tissue at the surgical site was still reddish (Figure 2B).

The patient’s oncologist was consulted, citing concerns that imatinib was interfering with the healing process. The oncologist agreed that the patient could discontinue imatinib, and the patient stopped taking it 12 days after the revision surgery.

At the postoperative examination 4 weeks after surgery (2 weeks after stopping imatinib), the soft tissue at the surgical site was healing uneventfully. The reddish soft tissue could only be observed at the site near tooth no. 20, and was much smaller in size relative to 2 weeks earlier (Figure 3).

At the 6-week postoperative examination (4 weeks after discontinuing imatinib), the soft tissue healed and covered the ridge at tooth no. 19 site completely. However, the ridge center was concave, with radiographic evidence of bone graft loss at the coronal portion due to the prior unhealed gingival tissue, which could not protect the bone graft from oral exposure (Figure 4). Another clinical examination of tooth no. 19 site was performed 7 months after the revision surgery. As shown in Figure 5A, the soft tissue was healed completely and the previous indentation at the tooth no. 19 site was filled. However, radiographic evidence of bone loss was still present (Figure 5B). Because the patient’s oncologist recommended only a 4-week pause in the imatinib therapy, all surgical procedures were postponed indefinitely, and the patient began taking imatinib again accordingly (4 weeks after pausing imatinib).

Discussion