Oral lichen planus and neurogenic inflammation: new observations and therapeutic implications from four clinical cases

Abstract

Oral lichen planus (OLP) is a usually chronic and relapsing mucocutaneous disease with unknown etiology. Immunosuppressive treatment is sometimes unsatisfactory. We describe four cases of reticular OLP localized on the internal side of cheek, in the territory innervated by sensory free endings of the buccinator nerve, poorly responding to immunosuppressive treatment (topical/systemic corticosteroids, topical cyclosporin). Addition of prazepam 10 mg/day to standard therapy achieved significant improvement and clinical healing in 30-40 days. Because of the complex interplay between the nervous and immune systems, neuroinflammation, acting through conventional axon reflex and/or indirect reflex mechanism involving localized efferent vasodilatory parasympathetic fibers, could have an important pathogenic role in OLP. Such hypothesis could explain, at least partly, the spreading of lesions in OLP primarily triggered (and possibly sustained) by infections, irritants, or autoimmunity. Moreover, neuroinflammation could have a relevant role in OLP related to psychosomatic diseases, where the nervous component is the primary trigger and the main pathogen responsible for the lesions observed. Benzodiazepines modulate neuroinflammation through central, and, possibly, peripheral action. In OLP patients with mild/subclinical psychological conditions, low doses may effectively modulate neuroinflammatory pathways that are not always completely inhibited by immunosuppressive treatment and can contribute to the persistence of inflammation.

Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

“…Then, we propose, in agreement with previous clinical observations referred to various cutaneous/mucosal pathological conditions , that a conventional axon reflex and/or an indirect reflex mechanism involving localized efferent parasympathetic fibers could be implicated (FIG. ).…”

“…). Axon reflex is a peculiar physiological mechanism caused by passage of nerve impulses from a sensory ending to the effector organ along divisions of the nerve fiber without traversing a “reflex center”, while the indirect pathway mechanism requires central processing of trigeminal input . The first mechanism appears more likely in our patient, because the clinical picture is not typical of indirect reflex (wider spreading of edema, discomfort and pain because of involvement of other trigeminal branches would be expected).…”

“…We diagnosed acquired vibratory angioedema (personal and familial history was negative for this condition), and suspected the possible involvement of neuroinflammation in its pathogenesis, on the basis of previous experience with such mechanism . Thus, we suggested therapy with amitriptyline 6 mg/day and bromazepam 0.6 mg/day.…”

Psychological profiles in patients with symptomatic reticular forms of oral lichen planus: A prospective cohort study

“…Pro‐inflammatory cytokines can access the central nervous system and interact with the cerebral cytokines network influencing the brain activity; in addition, the cytokines administration can promote depression, while anti‐inflammatory medications may decrease depressive symptoms, and depression interventions may be able to reduce inflammation . Peripherally, the local inflammatory response vs an unknown antigen may be responsible for the peripheral neuropathy in OLP . Furthermore, structural and functional changes in the peripheral nerve fibers may sustain the OLP chronic inflammation (the theory of neurogenic inflammation) and be responsible for the oral discomfort.…”

Lichen Planus Sparing the Extremity Affected by Poliomyelitis: The Profound Role of Neuroinflammation in Disease Development

“…The neurological system is in close relationship with the immune system by means of the sympathetic nerve traffic, hormones, neuropeptides, and cytokines (4). Changes in peripheral innervation and nociception in oral lichen planus as well as the therapeutic response to benzodiazepines suggest a possible role of neuroinflammation in disease etiopathogenesis (1,3).…”