Oral Lichen planus L43.8

Limited to the mucosal area of keratinizing and non-keratinizing squamous epithelia (intestinal mucosa and mucosa of the urogenital tract are not affected!) or occurring in the context of an integumentary lichen planus, polyetiological, multiform, patchy or plaque-like (also reticulated) whitish-keratotic or also rarely erosive or vesicular/bullous lichen ruber (especially oral and/or genital mucosa).

The autoantigen that triggers the migration of T cells into the epithelium in OLP is unknown (see lichen planus below). It is assumed that epidermal or dermal-epidermal antigens including desmogleins and BP180 (bullous pemphigoid antigen 180) are possible initiating antigens (evidence of type I/17 autoreactive T cells against Bp180 and DSg3 is available). Occasionally, humoral AK against these antigens are also detected. However, the antibodies have no acantholytic potential (DD against pemphigus vulgaris)

A co-pathogenic role of hepatitis C infections and autoimmune thyroiditis is being discussed (Schruf E et al. 2022).

An autoimmunological genesis can be assumed. In about 30% of patients with "vulvovagino-gingival syndrome", autoimmunological "concomitant diseases" such as diabetes mellitus, Hashimoto's thyroiditis (15%), vitiligo (5%), alopecia areata (4%), celiac disease, pernicious anemia, Sjögren's syndrome, idiopathic thrombocytopenic purpura are found.

Mechanotransduction: Mechanical stress plays a pathogenetic role in oral lichen planus. In patients with oral lichen planus, blood levels of angiotensin II are elevated, resulting in activation and upregulation of the mechanosensory receptor TRPA1 in both lesions and unaffected skin. TRPA1 is usually induced by mechanical stress and promotes keratinocyte proliferation and local immune responses. Repeated and prolonged mechanical stresses in the oral cavity, such as mechanical trauma due to dental surgery, friction from sharp tooth edges and poor oral habits, activate TRPA1 and exacerbate oral lichen planus by KP(Eisen D 2002).

Externals: Allergic reactions to amalgam or other materials used in dentistry (e.g. eugenol) have been discussed and proven in individual cases of oral lichen planus.

w:m = 8:2 (Daidona D et al. 2024)

The median age of onset at first diagnosis is between 40-60 years (11-94 years). In a larger study, the median age was 59.2 years.

Both monotopic oral and vulvovaginal LP tend to be chronic with continuous or discontinuous recurrent clinical courses over 3-10 years.

A mean duration of > 10 years (3-31 years) is reported for vulvovaginal-gingival syndrome.

Smoking does not appear to play a role in either the maintenance or the initiation of oral lichen planus.

Oral mucosa (mostly bilateral cheek infestation), tongue (especially lateral tongue areas), gums.

About 75% of lichen ruber patients show discrete or distinct oral and/or vulvo-vaginal involvement.

The gingiva is affected in about 10% of patients.

See also Lichen planus.

Oral mucosa(oral lichen ruber/planus):

• OLP I (white papule or plaque type, most common type >90% of OLP cases): Mostly streaky, punctate, annular, reticular, also flat whitish papules or plaques, which may confluent into large opal plaques, especially retroangularly and in the area of the entire dental ridge(Köbner phenomenon). A small papular mucosal type is less common (see illustration). Underlying erythema (of lichen planus inflammation) is not always visible (masking phenomenon of superimposed orthokeratotic keratinization of the mucosa). The changes are usually not painful. The red of the lips may also be affected, but may also be affected in isolation. Occasionally, brownish hyperpigmentation occurs. The tongue can be affected by extensive opal plaques, which are only more visible when viewed from the side. Parallel to this, a coarsening of the surface relief can be observed (as an expression of the diffuse lichenoid inflammation). Some patients (about 1%) report taste disturbances.
• OLP 1II (red or erosive type): second most common manifestation (<10% of OLP cases) of lichen ruber mucosae (see below lichen ruber erosivus mucosae). This is characterized by painful (especially when ingesting acidic food or drinks) flat erythema, erosions or flat ulcers. The main clinical symptom of the erosive type is "pain", which occurs promptly, especially with acidic food or drink. At 0.5-2.0%, erosive lichen ruber has a clear risk of malignant transformation. Although antibodies against Dsg are rare in OLP, they usually occur in erosive OLP!
• Type I/type II in various mixed forms.
• Lichen ruber mucosae is described as an "oral lichenoid reaction", which occurs in the immediate vicinity of amalgam fillings on the buccal mucosa, tongue or gingiva. Some authors postulate an independent entity (see notes below).
• Gingiva: Chronic desquamative gingivitis appears when the gingiva is affected. The "leukoplakic" aspect is often completely absent. Flat erythema or flat, very painful erosions appear, which increase in size during an acute attack and become symptomatic when acidic foods (e.g. orange juice) are consumed.

Genital mucosa:

• The genital mucosa is less frequently affected than the oral mucosa. The clinical symptoms are similar to those of the oral mucosa. Problems during sexual intercourse or burning discomfort when urinating usually lead to the doctor. A severe, chronic and scarring variant is referred to as"vulvovagino-gingival syndrome".

Aphthae: Rapidly developing, solitary or multiple, painful, 0.2-0.5 cm, inflammatory, low-elevation mucosal infiltrates with central fibrin-covered erosion (rarely ulceration) and erythematous margins.

Leukoplakia: Male>female; ubiquitous in oral cavity; preferentially retroangular, floor of mouth, margins of tongue, vestibule oris, edentulous alveolar ridge. Usually circumscribed or large, grayish to off-white foci with smooth or bumpy surface; histologic confirmation.

Pemphigus vulgaris: Typical is a chronic insidious onset, fluctuating between improvement and recurrence. Note: Blisters are often not seen in this localized stage; thus, the disease is usually not clinically evaluated as blistering. Frequently (> 50%!) first clinical manifestations in the oral cavity (erosive, painful stomatitis, fetor ex ore).

Mucosal pemphigoid: Recurrent, erosive, painful stomatitis with rapidly bursting, scarring healing blisters (blisters often not detectable) on the palate, cheeks and gingiva. Usually simultaneous involvement of the conjunctiva (always absent in lichen ruber mucosae).

Chronic ulcerative stomatitis: Rare erosive disease of the oral mucosa. Especially women are affected. Characteristic is a fluorescent pattern with IgG antibodies and nuclear pattern of basal and suprabasal keratinocytes.

Depending on the activity and extent of the lesions. Satisfactory results are only achieved with extensive symptoms through systemic therapy.

Smaller non-erosive lesions: In the case of non-erosive, clinically less troublesome lesions, only a mild local therapy with mild astringent stomatological agents (e.g. Tormentill astringent R255 ) or dexpanthenol solution (e.g. Bepanthen Lsg., R066 ) is necessary; if necessary, this may also be dispensed with. In the case of isolated oligo- or asymptomatic mucosal infestation, such a procedure would also be preferable.

Localized non-erosive infestation of the lips: As in most cases only minor symptoms occur, regular application of a grease pencil is recommended. A lip ointment containing lanolin is also pleasant. Light protection in summer!

Localized affection of the lips with clinical symptoms (burning, pain): Lanolin-containing lip cream as basic care, several times a day. Additive: Ciclosporin-containing external cream. A ready-to-use preparation can be recommended (Ikervis eye drops), which should initially be applied daily. Also here, light protection is required!

Large-area non-osseous foci: In case of large-area, isolated infestation of the mucosa, a consistent local therapy with vitamin A acid solution or gel R258 can be applied (apply gel or solution to the mucosa with a toothbrush and let it act for a few minutes). If necessary, alternate (or combine) with a 0.1% betamethasone oral gel(Betamethasone Valerate Adhesive Paste 0.1% NRF 7.11.) or prednisolone acetate paste (Dontisolon D Oral Healing Paste). Celestamine liquidum® which is left in the mouth for 2-3 minutes and then rinsed out has also proved effective.

Inflammatory, erosive foci (patients are considerably impaired in their quality of life by these often chronic, painful oral mucosal changes).

• Local therapy with topical glucocorticoids, e.g. with 0.1% betamethasone oral gel (betamethasone valerate adhesive paste 0.1% NRF 7.11.) , is possible as "first-step therapy".
• There is also good experience with clobetasol cream (e.g. Dermoxin cream applied to a gauze-wrapped mouth spatula and applied locally).
• Alternatively, aqueous prednisolone or /hydrocortisone solutions are recommended (e.g. Rp.: Nystatin 100KUI/Lidocaine 0.1/Prednisolone 0.1/ aqua purificata ad 100.0/ S: Apply mild well-tolerated prednisolone-containing solution 1-2x daily; or a combination preparation of hydrocortisone acetate and tetracaine hydrochloride - Rp.: hydrocortisone acetate 1.0/ propylene glycol 37.3/ tetracaine hydrochloride 2.0/ guaj-azulene 25% aqueous 0.05/ cremophor RH40 0.4/ peppermint oil 0.3/ panthenol solution 5% 40.0/ distilled water. Water ad 285,0/S: Mild well tolerated hydrocortisone containing solution 1-4 times daily). Spraying the lesions several times a day with a nasal spray containing Momethasone (Nasonex®-Supension) has proved successful.
• Good results have been described with a paste containing ciclosporin A(Ciclosporin A Adhesive Paste 2.5) and a 0.03% tacrolimus suspension (evidence level: B) (alternative: 1% pimecrolimus cream, which is better tolerated in the mucosal area). For this purpose, apply these externals to the lesion with a soft toothbrush or on a spatula wrapped in gauze and leave on for as long as possible. Treat 2-3 times a day.
• Topical preparations containing vitamin A acid are less suitable for this type of lesion (they have too strong an irritating effect!).

Remark! In case of pronounced clinical symptoms and chronicity, the (symptomatic) local treatment described above is not sufficient!

The treatment of first choice is the combination of acitretin and glucocorticoids. Acitretin (e.g. Neotigason) initially 0.5 mg/kg bw/day and prednisolone (e.g. Decortin H) initially 1 mg/kg bw/day p.o. Maintenance dose according to the clinic. The therapy must be carried out over weeks to months according to the clinical symptoms.

Alternatively: if not sufficient, combination therapy with azathioprine and systemic glucocorticoids is required: azathioprine (e.g. Imurek) initially 1.0-1.5 mg/kg bw/day and prednisolone (e.g. Decortin H) initially 1.0-1.5 mg/kg bw/day. Reduction of the dose according to the clinic.

Alternative in case of resistance to therapy: monotherapy with Ciclosporin A (3.0-5.0 mg/kg bw/day p.o.) or mycophenolate mofetil (e.g. CellCept 2.0 g/day p.o.).

Alternatively: methotrexate 10-15 mg/week p.o. As with other system therapeutics, months/years of therapy must be expected. Positive effects can be expected after 12 weeks of therapy.

Alternative: use of biologics (TNF-alpha blockers). 4-week laboratory controls are necessary.

Experimental: A therapy targeting TRPA1 could contribute to the stabilization of oral lichen planus.

In vulvo-vagino-gingival syndrome, the initial weight-adapted use of azathioprine (e.g. Imurek) 1.5-2.0 mg/kg bw/day p.o. is recommended , possibly in combination with a glucocorticoid in an initially medium dosage (e.g. prednisolone 0.5 mg/kg bw/day p.o.). Subsequently, clinically adapted lower dosage (5.0-7.5 mg/day p.o.).

Please note! All therapies presented here are "off-label use" applications. Scientific proof of the superiority of systemic therapy over local therapy has not yet been provided for oral (or vulvo-vaginal) LP.

There is an increased risk (1-3%) of developing oral squamous cell carcinoma in oral LP. The WHO classifies oral lichen planus as a "premalignant condition" (van der Meij EH et al. 2003).

An increased risk of squamous cell carcinoma was also found for vulvar lichen planus. The rate of inguinal metastasis and recurrence is high, as is the disease-related mortality rate.

Both oral and vulvo-vaginal lichen planus are associated with an increased candidiasis rate.

Chamomile extracts: Chamomile rinses(Matricariae flos) applied several times a day can be used in natural medicine.

Alternative: Aloe vera: In small clinical studies (multiple) good effects are described for oral as well as genital lichen planus with locally applicable aloe vera preparations (e.g. 0.5% aloe vera gel) (Rajar DU et al. (2008).

Alternative: Local therapy with a mixture of eucalyptus oil, fennel oil, levomenthol, clove oil, peppermint oil, sage oil, star anise oil, thymol, cinnamon oil as offered in ^{Salviathymol®} N.

Alternative: clove oil: brushings with clove oil(Caryophylli floris aetheroleum).

Dietary measures: In the case of erosive Lichen planus mucosae, it is recommended to avoid pungent spices, fruit acids (vinegar, citrus fruits, wine and other spirits) of highly salted foods, as they cause a burning of the oral mucosa. Pay attention to sufficient nutrition (vitamins, minerals)!

When cleaning teeth, it is recommended to use a soft toothbrush and a mild toothpaste.

The formation of a compact hyperkeratosis is responsible for the leukoplakic aspect of mucosal lichen ruber. The water-retaining horny layer swells, resulting in the opalescent milk glass effect. The surface becomes intransparent white.

Some authors delineate oral lichenoid reaction (OLR) as an immunologic hypersensitivity reaction clinically and histologically "similar" to lichen planus mucosae, to which a specific trigger can be assigned. These include drugs (NSAIDs, antihypertensives, retroviral drugs), contact allergens (dental materials, amalgam, copper, gold, eugenol), which by definition can be found up to 1.0 cm from the OLR.

The syndromal occurrence of oral lichen ruber, arterial hypertension and diabetes mellitus is called"Grinspan syndrome". The occurrence of squamous cell carcinoma in lesional oral mucosa has been reported (Kökten N et al. 2018).

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