Oral diseases caused by taking medicine (Part 3) - lichenoid reaction

The oral ADEs mentioned above include erosion, drug-induced gingival hypertrophy, and dry mouth, which damage the health of teeth, periodontal tissues, and salivary glands respectively. The oral ADE we will talk about today is the "highlight" of oral ADEs - drug-induced oral mucosal disease.

This is not actually a disease, but a category of diseases. In other words, drug-induced oral mucosal diseases have many causes and complex manifestations. Drug-induced oral mucosal diseases include lichen planus/lichenoid reactions, aphthous ulcers, bullous diseases, pigmentation, keratosis/epithelial hyperplasia, paresthesia, etc. It affects the most inconspicuous, but actually very important organ in the entire oral cavity - the oral mucosa. It is said to be the most inconspicuous because you usually don't feel the significance of its existence; but it is very important because once it has problems, such as blisters, ulcers, etc., you will definitely have problems eating.

Lichen planus and lichenoid reactions

Lichen planus (LP) is one of the common inflammatory diseases that affect the health of the skin and oral mucosa. It is essentially an immune process, namely the destruction of basal cells in epithelial tissue mediated by T cells.

Oral LP mainly occurs in the buccal mucosa, tongue, and gums, and manifests as white streaks (i.e., Wickham lines ) or papules accompanied by erythema or erosion and ulceration, which are bilaterally symmetrical.

It is known that many drugs can induce lichenoid hypersensitivity reactions (LHR) in the skin, and these skin changes are difficult to distinguish clinically or pathologically from idiopathic cutaneous LP. Cutaneous LHR mainly occurs on the trunk and limbs and can manifest as a rash characterized by purple, pruritic keratotic papules and plaques. It is currently speculated that the active thiol groups in the chemical structure of drugs such as piroxicam , sulfasalazine , and glipizide may induce LHR. Therefore, these drugs may also cause oral LHR, similar to idiopathic oral LP.

Source: References

Pathogenesis of oral LHR

In the past, two classes of drugs that were thought to be associated with oral LHR were nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs (beta-blockers, ACE inhibitors, and diuretics, especially hydrochlorothiazide). Sulfonylurea antidiabetic drugs (such as tolbutamide and glipizide), antifungal drugs (such as ketoconazole), anticonvulsants (such as carbamazepine), immunomodulatory drugs (such as gold preparations and penicillamine), sulfasalazine, allopurinol, and lithium have also been reported to cause oral LHR.

The triad of oral LP, diabetes mellitus, and hypertension was considered a clinical manifestation of Greenspan syndrome at the 1963 Congress of Dermatology. It is now generally accepted that oral LHR is induced by hypertension in particular and possibly by drug therapy for diabetes.

One theory regarding the pathogenesis of LHR is that susceptible individuals have polymorphisms in cytochrome (CYP) 450 enzymes, which may affect CYP metabolism of certain drugs.

Diagnosis of LHR

It is often difficult to reach a consensus on the diagnostic criteria for LHR, in part because once LHR changes are established, they may persist even after drug withdrawal unless they are treated rigorously. However, some scholars have suggested that a history of current LHR-inducing medication combined with histopathological findings consistent with LHR changes is sufficient to make a diagnosis.

(To be continued)

References

[1] Yuan A, WooSB. Adverse Drug Events in the Oral Cavity[J]. Dermatol Clin, 2020, 38(4): 523-533.