Dentine hypersensitivity-like tooth pain associated with the use of high-dose steroid therapy.

Although corticosteroid provides many clinical benefits, it may cause a range of side effects. A 47-year-old female patient presented with a complaint of pain from her teeth, triggered upon taking cold, hot, and sweet food and drink. From her medical history, she was previously diagnosed with ulcerative colitis. She consequently developed pyoderma gangrenosum, and high-dose prednisolone was administered to treat this condition (prednisolone 30 mg bd for 4 months followed by tapering dose 5 mg/week). She claimed the pain started at the end of steroid therapy. The pain mimicked symptoms of dentine hypersensitivity, but without the presence of the clinical signs associated with hypersensitivity, suggesting that the pain was steroid induced. Patients in this condition will find that their dietary choices will be limited and effective oral hygiene be impeded. Reassurance and advising patients to maintain oral hygiene are the most appropriate treatment as this condition would eventually wear off with time.

INTRODUCTION

Corticosteroids are widely used in the treatment of severe asthma and chronic obstructive pulmonary disease, severe allergic reactions, organ-transplant recipients, and autoimmune disorders.[1] Although it is a popular choice of drug and provides many clinical benefits, it may also cause a range of side effects. The manifestation of the side effects depends on its route of administration and duration of use.[2]

According to the data of eHealthMe (2018) by Food and Drug Administration (FDA) reports, 247,408 people were reported to have side effects when taking prednisolone, a type of corticosteroid.[3] Among them, 214 people (0.09%) suffer from tooth pain. Interestingly, there is no documented evidence in the academic literature that addresses sensitive teeth as an adverse effect of steroid therapy. In contrast, there are various informal reports on social media (personal blogposts and Facebook pages) from patients who were on steroids that claimed they experienced sensitive teeth after taking the medication. To quote the post from one of the many personal blogposts at http://www.moonsandspoons.com/prednisone-and-sensitive-teeth-my-imagination/, “My doctors and I are definitely not on the same page here. I was frustrated in discussing this with my doctors. Perhaps I was frustrated because it really wasn't a discussion; it was just my question and their answer–no relevance. But my experience told me different. How can I not believe that the tooth sensitivity is connected to the steroids? The only thing that I believe made a notable difference in my sensitivity was when my prednisone dosage dropped, and my body had time to work the steroids out of my system. But before that happened, eating (and sometimes breathing) was a bit of a struggle. I also have to include that I was doing a version of the autoimmune protocol diet in the last 5 months when I have noticed an improvement in my teeth. My dosage lowering and new diet/lifestyle do coincide.”

Shoji et al. surveyed 220 patients who had undergone steroid therapy to determine the potential relationship between steroid therapy and dentine hypersensitivity (DH)-like tooth pain.[4] The prevalence of tooth pain in these patients was 17.7%. They concluded that steroid therapy can evoke DH-like tooth pain during treatment as a positive correlation was found between steroid dose and pain score.[4]

To our knowledge, this case report is the first to record the occurrence of DH-like tooth pain in a patient who had been on high dose of prednisolone.

CASE REPORT

A 47-year-old female patient attended our endodontic specialist clinic complaining of generalized pain from her teeth. The pain started a few months ago (sometime from April 2017). It was triggered upon taking cold, hot, and sweet food and drink. At the initial stage, she reported that even taking in a large breath through her mouth could evoke the pain. The pain was throbbing, severe in nature, and was continuous for more than a few minutes before it subsided. She claimed that the pain occurred in multiple teeth, and she was not able to pin point any particular tooth. Because of the pain, she refrained herself from taking cold, hot, or sweet food. She was not on painkillers as the pain would only appeared upon stimuli.

The medical history revealed that the patient was diagnosed with ulcerative colitis in 2008 and had been on azathioprine (75 mg) and mesalazine (1 g tds). She suffered from a severe case of pyoderma gangrenosum in November 2016 and had to be hospitalized for 4 months. A high dose of prednisolone (30 mg bd) for 4 months was administered to treat this condition followed by tapering dose of 5 mg/week until the end of May 2017 when the pyoderma gangrenosum lesion healed. The patient was a medical practitioner (with a doctorate degree in pharmacology), so she was able to give an accurate medical history.

During the examination, the patient kept complaining of severe pain when short blast of cold air from the 3-in-1 syringe was used to dry the teeth for inspection. Clinical examination revealed that she had good oral hygiene, with minimal plaque accumulation at the upper anterior teeth [Figure 1a and b]. The gingiva appeared pink and healthy. Basic periodontal examination revealed probing depths of normal limit (2–3 mm).

Figure 1

(a) Right buccal view at the first visit, (b) left buccal view at the first visit, (c) occlusal view of mandibular area at the first visit, (d) preoperative periapical radiograph of tooth 36

Defective amalgam restoration was noted on the disto-occlusal aspect of tooth 36. The restorations on teeth 15, 27, 45, and 47 were sound [Figure 1c]. The rest of the teeth had normal clinical crowns without the presence of attrition on the occlusal surfaces [Figure 1c]. Minimal root exposure could be detected on tooth 32 only, while no evidence of abrasion was observed from any of the teeth [Figure 1a and b]. Responses from sensibility tests (cold test and electric pulp test) indicated that tooth 36 was vital. It was tender neither to percussion nor palpation. The periapical radiograph showed that the restoration was near the pulp horn, but there was no abnormality at the apices [Figure 1d].

The differential diagnosis for this patient was DH although we could not ascertain the possible etiology for the condition at the first visit. The finding from patient's dental history was insignificant. The treatment plan was to replace the amalgam restoration on tooth 36 to rule out possible pulpal pain followed by treatment for DH. Local anesthesia (scandonest 2%) via inferior dental block on the lower left side was administered. Upon removal of the amalgam using a high-speed handpiece with water, the patient experienced intense generalized pain from the other teeth, and the amalgam filling was removed intermittently until completion. The Visual Analog Scale score at this time was 10/10. The patient could not stand the pain, and a zinc oxide eugenol temporary filling was placed [Figure 1c]. Calcium hydroxide was not placed as there was no pulpal exposure and the pulpal floor appeared adequate.

Based on the differential diagnosis, it was decided to apply sodium flouride (SF) varnish (Colgate® Duraphat® Varnish 50 mg/ml dental suspension 2.26% SF) to all teeth to manage the pain. Application of the varnish was performed by quadrant starting from the upper right, upper left, lower left, and lower right quadrant. The buccal and lingual surfaces of all the teeth in each quadrant were dried with gauze after which the varnish was applied with the use of a disposable brush to form a single, uniform, and thin coat over the cervical area of the teeth. She was advised to use the desensitizing toothpaste every time she performed toothbrushing. The patient was reviewed 3 days later, and the application of varnish was repeated. Another similar application of the varnish was repeated 3 days after the second visit. She reported that the pain became more bearable after the varnish was applied although it did not disappear completely if she took cold or hot drink.

The patient was then reviewed 6 months after the last visit. She reported that she was now able to tolerate cold and hot food and drink much better than previously. Clinical examination revealed intact temporary filling on tooth 36. There was more calculus accumulation at the lingual areas of the lower teeth and upper posterior teeth [Figure 2a and b]. This inability to remove plaque totally may be due to the pain the patient experienced during toothbrushing throughout the “active pain” period. Tooth 36 was restored with composite filling, and all teeth were scaled and polished during this visit [Figure 2c and d] without any complications. The varnish application procedure was not repeated at this visit.

Figure 2

(a) Right buccal view at 6 months' review, (b) left buccal view at the first visit at 6 months' review, (c) right buccal view after scaling, (d) tooth 36 after it was restored with composite

DISCUSSION

Prednisolone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases (such as moderate allergic reactions), some autoimmune diseases, and (at higher doses) some types of cancer, but it has significant adverse effects.[5] The dental-related side effects due to steroid that had been studied include pulp chamber and root canal obliteration and root resorption during orthodontic tooth movement under the effect of corticosteroid.[6789] Corticosteroid treatment has also been shown to interfere with orthodontic tooth movement rate and tissue reaction.[10]

DH is characterized by short, sharp pain arising from the exposed dentine in response to stimuli, typically thermal, evaporative, tactile, osmotic, or chemical, which cannot be ascribed to any other dental defect or pathology.[11] In this case, the symptom of pain experienced by the patient was similar to DH as the pain aroused in respond to thermal and sweet food/drink that cannot be associated with any dental defect, such as evidence of excessive or traumatic tooth brushing, poor oral hygiene, exposed dentine or root surfaces, and evidence of tooth surface loss.[12] As such, it was described in this report as DH-like tooth pain. This tooth pain was strongly suspected to be associated with high-dose prednisolone as the patient started experiencing the pain after the intake. This suspicion was supported by a particular case report by Symons and Symons that described the cases of pulpal obliteration related to long-term glucocorticosteroid medication.[8] Out of the three cases portrayed in the report, one patient who received steroid dosages exceeded 30 mg/day for that year (Case 2), complained of dental sensitivity to cold, and was unable to consume cold foods such as ice cream or iced drinks during the 1st year of medical therapy, similar to the symptoms experienced by the patient in our case.[8] Another strong evidence so far is from Shoji et al's. study. The survey of 220 patients in this study suggested a positive correlation between steroid dose and “DH-like” pain score experienced by the patients during the therapy.[4] This finding provides validation of anecdotal information related to tooth pain that occurs as a side effect of steroid therapy. This study had also managed to capture the description of pain experienced by these patients on steroid which mimic the symptoms of DH but with some differences, i.e., (i) the pain is not transient, but continuous and severe, (ii) the pain is triggered by both hot and cold drink/food, (iii) the pain occurs in multiple teeth (not localized to any particular tooth), (iv) the pain arises from tooth without obvious root exposure, (v) standard treatment for DH is effective only temporarily, and (vi) the pain diminishes or resolves with reduction or discontinuation of the steroid.[4] These descriptions were similar to the symptoms experienced by the patient in this case.

DH-like tooth pain as a side effect of steroid therapy is a rare occurrence. The report from the FDA indicates that prevalence of those on prednisolone and are reported suffering from “sensitive teeth” is very low, i.e., 0.09%.[3] It occurs more frequently among patients who are female, aged 60 years old and above, have been taking the drug for more than 1 month, and who also take the drug together with Zometa (zoledronic acid).[3] Electronic searches via search engines such as PubMed, MEDLINE, Google Scholar, Scopus, and Cochrane Library revealed that it had been infrequently reported in the literature.[481314] When it was described as one of the side effects, there was no detailed description on the characteristic of pain, possibly because the patients in the study were reviewed by medical practitioners.[1314]

Steroid has strong anti-inflammatory and immunoregulatory effects and has not been shown to induce pain or increase pain sensation in any organ.[4] In fact, it has been used in the management of dental pain.[15] Therefore, the mechanism underlying the DH-like tooth pain is currently not known. Endo et al. carried out an experimental study in rats and reported that, following steroid administration, particular glial cells were activated in the subnucleus caudalis of the trigeminal sensory complex of rats, where trigeminal primary afferent fibers innervating orofacial areas project.[16] This finding indirectly shows the possible relationship between steroid administration and trigeminal nociception.[4] However, there is no explanation why pain only occurs to the teeth without involving other oral tissues as the trigeminal primary afferent fibers from the subnucleus caudalis innervate all the oral tissues including the dental pulp. Shoji et al. hypothesized that it could be that a peripheral afferent nerve fiber mechanism (rather than the central afferent fiber) is the likely mechanism that causes the teeth to be sensitive to stimuli.[4] In laboratory studies, steroid had also been shown to alter the pulpal tissue in which it caused the pulp chambers and root canals to become narrower and obliterated.[1718] In his study, Kamatani observed that the cell-rich zones and subodontoblastic cell-free zones in the pulp tissues became distinctive when it was cultured with dexamethasone (a type of corticosteroid) as compared to the normal pulp in which this layer was either indistinct or absent.[17] This caused an accelerated dentin deposition which could explain the cases of pulpal obliteration. The dentine deposition in turn caused pulp stone formation in vital teeth. Symons and Symons suggested that acute dental pain suffered by patients who were on steroid could be due to pulp stone formation which had been reported to cause acute dental pain.[8]

Although DH-like tooth pain associated with steroid is not common, this case report is meant to highlight the pain characteristic suffered by the patient and its management. This in turn will create awareness for the dentist to reassure the patient and recommend treatment measures for the tooth pain. Misdiagnosis of the cause of this pain may result in unnecessary loss of pulp vitality or even extraction.[8] Although the actual reason for tooth loss was not explored, Walsh et al. reported that half of the patients in their study who were on oral corticosteroids had no natural teeth compared with 39% in the control population.[19]

The main proposed mechanism for DH suggests that pain sensation is induced by fluid movement within the dentinal tubules in response to external stimuli (either hot, cold, mechanical, evaporative, or osmotic stimuli) on exposed dentine.[12] The mineralocorticoid activity of prednisolone was reported to induce the peripheral edema in the skin and, if this influences the pulpal tissues, then the induced edema in the confined space of the pulp chamber could facilitate fluid movement within the dentinal tubules in response to the external stimuli causing DH-like pain.[4] The pain induced by steroid therapy is not transient but continuous, suggesting that the stimuli evoke neurogenic inflammation mediated by sensory neuropeptides such as calcitonin gene-related peptide and substance P.[4]

Taking the corticosteroids may cause a range of side effects. However, the medications give significant benefits to many different diseases and conditions. Consequently, patients are left with no other choices but to take the drug. As the possible cause of tooth pain in this case is likely due to internal changes of nociception, the standard treatment generally performed for DH will only provide temporary pain relief. SF varnish is one of the in-office desensitizing agents used to occlude and seal the exposed dentinal tubules.[20] It creates a barrier and therefore reduces the dentin permeability and consequently DH. The varnish worked for this patient to a certain extent, but it was not able to relieve the pain completely. The temporary relief in pain may be due to coating of the varnish (which contains natural resins) on the surfaces of the teeth that provide barrier effect against external stimuli that induce the pain.[21] Another possibility could be due the placebo effect that the patient felt the improvement of the pain after the application of varnish. At 6 months' review, the patient reported that she had no longer experienced the intense pain as previously. She noticed that the pain now had diminished over time. During this review, plaque accumulation was observed especially at the lower anterior region which was not present at the initial appointment. The patient reported that she could not really clean those teeth thoroughly due to the hypersensitivity when brushing.

Patients need to be reassured that the pain is temporary and will disappear over time after discontinuation of the drug. Advice to the patients can include; (i) take food and drink at room temperature, (ii) drink from a straw if they want to take cold drink, and (iii) use warm water during toothbrushing. It is very important to emphasize on maintaining good oral hygiene as they may compromise on toothbrushing due to the pain evoked by cold water. Six-monthly review is essential to maintain the patient's oral health and prevent the development of any oral health-related disease.

CONCLUSIONS

DH-like tooth pain can occur as one of the adverse effects of steroid therapy. This case report highlights the pain characteristic suffered by a patient and its management. The pain bears similarity to the pain arising from the condition of DH, but it is distinguished by the severity of pain occurring in multiple vital teeth without obvious root exposure. Patients who suffer from this adverse effect may find that their dietary choices are limited, and effective oral hygiene may be impeded.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Ministry of Higher Education Research Grant FRGS/1/2015/SKK14/UKM/02/1 funded this study.

Conflicts of interest

There are no conflicts of interest.