Introduction

Oral lichenoid drug reactions (OLDR) characterized by white striae and erythematous or ulcerative area that erupts after administration of drugs such as angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), hypoglycemic drugs, penicillamine, etc. (1). The oral lesion of OLDR is similar to OLP both clinically and histopathologically (2). Difficulties in distinguishing between these two diseases resulted in difficulties in treatment and management of the lesions. However, the diagnosis of OLDR is rendered when oral lesions erupt after administration of the drugs and the lesions can be resolved after withdrawal of suspected drugs. Oral lichenoid contact lesions (OLCL) are in direct contact with offending agents such as amalgam or metal restorative materials. When the amalgam restoration or metal restorative materials are removed, the lesions are gradually resolved. However, replacement of restorative materials in OLCL is still controversial (3). Moreover, not all cases can be treated successfully, particularly in cases with multiple drugs administration or OLDR being concurrent with OLCL. This presented case was one of both OLDR and OLCL that was a challenge to manage. Various topical steroids still remain the first line of therapy to reduce pain and inflammation in this case as well as medical consultation. There is no specific treatment in refractory cases of OLDR and OCCL. However, the withdrawal of a suspected drug is useful during the treatment of refractory cases and can enhance healing of the lesions (4). A long-term follow-up is needed to improve the quality of life of the patient and to detect early lesions, should malignant transformation occur. To our knowledge, this was the first case report that showed the palliative treatment of refractory oral lesions with potent topical steroids for 7 years without side-effects.

A case report

A 54-year-old female was referred to the Oral Medicine clinic at the Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand in 2006 with a chief complaint of pain on the gingiva, the right and the left buccal mucosa for 5 years. She experienced pain when eating hot and spicy food. The otorhinolaryngologist treated her with pimecrolimus (Elidel) cream 1%, sore mouth gel, triamcinolone acetonide 0.1% orabase and Kamistad gel. Kamistad gel is an oral therapeutic gel with ingredients of Chamomile flower extract and Lidocaine HCl which is indicated for the treatment of painful and inflammatory processes of the oral mucous membrane was also treated, but the oral lesions showed only slight improvement. Triamcinolone acetonide injection (Kenacort) 10 mg/ml was also injected into the lesion 4 times, but no improvement. Her physician referred this patient with the histopathological report of oral lichen planus with no malignancy change from the biopsy specimen from the buccal mucosa. The skin biopsy from her leg was also done by her physician and it was pigmented purpuric dermatitis (PPD). All patch tests were negative at first. Surprisingly, 4 years later, the patch test showed positivity to mercury and palladium. Anti-HBs was positive with 138 mIU/mL, whereas anti-HCV was negative. Investigations of serology for autoimmune disease showed all negative for LE cells, antinuclear factor and anti DNA.

Regarding systemic diseases, she had a history of hypertension, dyslipidemia, subclinical hypothyroidism and arthritis. Her medications were Atorvastatin calcium ½ tab OD, Hydrochlorothiazide 50 mg, ¼ tab OD, Valsartan ½ OD, Eltroxin (levothyroxine) 0.1mg, 1 tab OD, Difflam lozenge 3 mg 1 tab tid pc and Diclofenac potassium 1 tab OD.

Oral findings in this case at the first visit to the Oral Medicine clinic, Faculty of Dentistry, Chulalongkorn University revealed ulcerative, erythematous lesions with white striae covered with pseudomembranes on the right and the left buccal mucosa (Figure 1 a, b). Her gingiva showed generalized fiery red on marginal and attached gingiva. Scraping from the surface of the lesions and using potassium hydroxide 10% was positive for both hyphal and yeast forms of Candida. The diagnosis at the initial visit was oral lichenoid drug reaction (OLDR) with candidiasis. Because the oral lichen planus-like lesions erupted after using medications mentioned above the diagnosis of OLDR was established. We suggested to her physician to change the medications and treated her oral lesions with fluocinolone with clotrimazole gel 0.1%, sodium bicarbonate mouthwash and folic acid 5 mg, 1 tab bid. After that, her physician changed diclofenac to tenoxicam one month later. However, her symptoms remained the same so the fluocinolone acetonide 0.1% in solution was used instead fluocinolone with clotrimazole gel 0.1%. Two months later, her symptoms showed approximately 50% improvement, but the right and left buccal mucosa to retromolar areas showed ulcers covered by yellowish pseudomembrane and surrounded with white striae. Dexamethasone mouthwash 0.05% was used for the treatment. Antihypertensive drug (Hydrochlorothiazide) was recommended to be replaced by others. After the replacement, hydrochlorothiazide with valsartan for 4 months, the lesions showed improvement. The potent topical steroids such as clobetasol propionate 0.05%, fluocinolone acetonide 0.1% orabase were used to treat the oral lesions.

Figure 1 a, b First visit, ulcerative and erythematous lesions with white striae covered with pseudomembranes on the right and the left buccal mucosa

In August 2007, her gingival and the right buccal mucosa showed marked improvement, but the left buccal mucosa showed round papillomatous-like lesions, size 0.5x0.5 cm. and 0.3x0.3 cm. with red color (Figure 2 a, b). Biopsy specimen was taken from this area and the histopathological report was non-specific ulcer with chronic inflammation. The sections revealed soft tissue with denuded epithelium showing fibrinous exudate coverage. Large amounts of superficial polymorphonuclear leukocyte infiltration were seen. A number of new forming blood vessels, plasma cells as well as lymphocytes were seen in the area (Figure 3).

Figure 2 a, b The right buccal mucosa showed improvement. The left buccal mucosa showed round papillomatous-like lesions, size 0.5x0.5 cm. and 0.3x0.3 cm. with red color

Figure 3 The sections reveal soft tissue with denuded epithelium showing fibrinous exudate coverage. Large amount of superficial polymorphonuclear leukocyte infiltration is seen. Numbers of new forming blood vessels, plasma cells as well as lymphocytes are seen at the area.

In May 2009, the patient was treated with valsartan, levothyroxine sodium, and simvastatin. Her dentist replaced the amalgam restoration on the left mandibular second molar with a full porcelain crown. Generalized fiery red gingiva, the right and left buccal mucosa flared up with pseudomembrane covering the surface of the lesions (Figure 4 a, b, c). Triamcinolone acetonide 0.1%, mouthwash, clobetasol propionate 0.05% orabase, dexamethasone 0.05% mouthwash were used to treat the lesions. The patient was referred to the Oral and Maxillofacial Surgery department for CO₂ laser. After the treatment with CO₂ laser 5 watt for 2 minutes twice, the oral lesions showed improvement (Figure 5 a, b, c).

Figure 4 a, b, c All gingiva, the right and the left buccal mucosa flared up particularly pseudomembrane covered on the surface of the lesions. Her gingiva was generalized fiery red with inflammation

Figure 5 After the CO2 laser treatment, the lesions showed improvement

In November, 2013, the left mandibular second molar was extracted by her dentist but the lesions still persisted and flared up. Direct and indirect immunofluorescence tests were assessed to exclude the lesions from oral pemphigus or mucous membrane pemphigoid because the oral lesions on the gingiva and buccal mucosa were similar to those lesions. The specimen was taken from the right buccal mucosa and indirect immunofluorescence report was negative to circulating IgG anti-basement membrane zone antibody. Direct immunofluorescence study showed negative findings to IgG, IgA, IgM, C3 and fibrin.

Discussion

Patients with many systemic diseases and taking multiple medications can have severe OLDR.

Hydrochlorothiazide, levothyroxine, NSAIDs can induce severe and chronic OLDR (1). The diagnosis criterion for OLDR is the eruption of oral lesions after taking suspected medications. The patient described here had been taking multiple medications including hydrochlorothiazide, levothyroxine and NSAIDs which have been reported for inducing severe and chronic OLDR (1).

The diagnosis of OLCL was made when the lesion appeared after direct contact to dental restoration such as amalgam or metal crown. With the removal and replacement of the suspected causative material, the majority of such OLCLs resolved within several months (1). The anatomy of the buccal mucosa with no mucobuccal fold might affect the successful treatment in this case. The direct absorption of topical steroid when the buccal mucosa is close to the teeth might not occur properly. Topical steroids application in long-term treatment of oral lichenoid lesions should be considered. However, continued use of potent topical steroids has been found to be useful in the management of severe oral lesions in these patients with many systemic diseases. No serious side-effects from treatment with topical steroids for oral lichenoid lesions in this case. Moreover, carbon dioxide laser can be used as an alternative treatment in this refractory case. However, maintaining good oral hygiene should be considered during follow-up.

Ethical considerations for dentists during management of recalcitrant oral lesions should be taken into account. The lesion may resolve if amalgam filling is replaced by composite resin (5). The procedure of crown preparation for full porcelain might be affecting the surrounding tissues and could trigger the lesions. However, replacing amalgam fillings or changing a metal crown is not always successful but the dentists should consider it during management of such patients with OLCL. Therefore, patients should be informed of the possibilities of positive or negative outcomes before replacement of the restoration or the crown. Positivity to patch testing was an inconsistent and generally weak predictor of improvement following amalgam removal (6). The cooperation of oral medicine specialists, other specialties and physicians is important during management of severe oral lesions. A long-term follow-up is needed to improve the quality-of-life in the patient with refractory oral lesions.

Conclusion

OLDR and OLCL have been known for a very long time in oral medicine and a complete cure of the lesions is very difficult to achieve. Treatment modalities such as potent topical steroids and drug replacement are standard of care in OLDR cases. We presented a refractory case with OLDR and OLCL who was indeed a challenging one to treat and manage. Continuous treatment of refractory oral lesions with potent topical steroids and CO₂ laser showed no serious side-effects during the long-term follow-up. This was the first case report that showed the palliative treatment of oral lesions with potent topical steroids for 7 years without side-effects. Therefore, the treatment modalities in this case report could improve the quality-of-life in patients with many systemic diseases.