Lichen planus mucosae 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).

Unknown, see below. Lichen planus.

A pathogenetic role of hepatitis C infections is discussed.

An autoimmunological genesis is to be assumed. In about 30% of patients with a "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.

It has been discussed, and in individual cases proven, that oral lichen planus is associated with allergic reactions to amalgam or other materials used in dentistry ( e.g. eugenol).

w:m = 2:1

The mean age of onset of the disease is between 40-60 years (11-94 years). In a larger study the median age was 59.2 years.

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

For the vulvovagino-gingival syndrome a mean duration of disease of > 10 years (3-31 years) is reported.

Smoking does not appear to play a role in either conversation or in triggering 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.

S.a. Lichen planus.

Oral mucosa(orallichen ruber/planus):

• Type I (white papule or plaque type): Mostly striated, punctate, annular, reticular also planar whitish papules or plaques, which may confluence especially retroangularly and in the area of the entire dental cusp(Köbner phenomenon) to large opal plaques. A small-papular mucosal type is less common (see Fig.). Underlying erythema (of lichen planus inflammation) is not always found visibly (covering phenomenon of overlying orthokeratotic mucosal keratinization). The changes are usually not painful. The red of the lips may be involved, but may also be affected in isolation. Occasionally, brownish hyperpigmentation develops. The tongue may be affected by both areal opal plaques, which are better seen only with lateral vision. In parallel, coarsening of the surface relief may be observed (reflecting diffuse lichenoid inflammation). Some patients (about 1%) report taste disturbances.
• Type II (red or erosive type ): second most common manifestation form of lichen ruber mucosae (see below lichen ruber erosivus mucosae). Painful erythema, erosions or ulcers appear on the surface (especially after ingestion of acidic food or drinks). The leading clinical symptom in the erosive type is "pain", which occurs promptly, especially with acidic food or drink. The erosive lichen ruber has a clear risk of malignant transformation with 0.5-2.0%.
• Type I/Type II in different mixed forms.
• Lichen ruber mucosae is described as an "oral lichenoid reaction", which occurs in the immediate vicinity of amalgam fillings on the buccal buccal mucosa, tongue or gingiva. Some authors postulate an independent entity (see notes below).
• Gingiva: When the gingiva is affected, chronic desquamative gingivitis impresses. The "leukoplakic" aspect is often completely absent. Erythema or very painful erosions appear, which increase in size during the acute episode and become symptomatic when acidic foods are consumed (e.g. orange juice).

Genital mucosa:

• The genital mucosa is less commonly affected than the oral mucosa. The clinical symptoms are analogous to those of the oral mucosa. Usually, problems during sexual intercourse or burning discomfort during urination lead to the doctor. A severe, chronicized and scarring variant is called"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 first choice therapy is the combination of acitretin and glucocorticoids. Acitretin (e.g. Neotigason) initial 0.5 mg/kg bw/day and prednisolone (e.g. Decortin H) initial 1 mg/kg bw/day p.o. Maintenance dose according to clinic. The therapy must be carried out over weeks to months according to the clinical symptoms.

Alternatively: if not sufficient, a combination therapy with azathioprine and systemic glucocorticoids is necessary: Azathioprine (e.g. Imurek) initial 1.0-1.5 mg/kg bw/day and Prednisolone (e.g. Decortin H) initial 1.0-1.5 mg/kg bw/day. Dose reduction according to clinic.

Alternatively 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 systemic therapeutics a months/years of therapy must be estimated. Positive effects can be expected after 12 weeks of therapy.

Alternative: Application of biologicals (TNF-alpha-blocker). 4-week laboratory controls are necessary.

In the case of 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.).

Notice! All therapies presented here are "off-label-use" applications. The scientific evidence of superiority of systemic therapy over local therapy has not been demonstrated for oral (or vulvo-vaginal) LP.

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

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

1. Boyce AE et al (2009) Erosive mucosal lichen planus and secondary epiphora responding to systemic cyclosporine A treatment. Australas J Dermatol 50:190-193
2. Corrocher G et al (2008) Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus. J Clin Periodontol 35:244-249
3. Kökten N et al (2018) Grinspan's syndrome: A Rare Case with Malignant Transformation. Case Rep Otolaryngol doi: 10.1155/2018/9427650.
4. Lauritano D et al. (2016) Oral lichen planus clinical characteristics in Italian patients: a retrospective analysis. Head Face Med 12:18.
5. Mehlika B et al (2014) Contact allergic lichenoid reaction to eugenol presenting as lichen planus mucosae. Allergo J Int 23: 14-17
6. Mansourian A et al (2011) Comparison of aloe vera mouthwash with triamcinolone acetonide 0.1% on oral lichen planus: a randomized double-blinded clinical trial.Am J Med Sci 342:447-451.

7. Mozafari N et al (2022) Hypertrophic lichen planus on lip mimicking SCC. Clin Case Rep10:e6191.

8. Ohno S et al (2011) Enhanced expression of Toll-like receptor 2 in lesional tissues and peripheral blood monocytes of patients with oral lichen planus. J Dermatol 38:335-344
9. Poomsawat S et al (2011) Overexpression of cdk4 and p16 in oral lichen planus supports the concept of premalignancy. J Oral Pathol Med 40:294-249
10. Rajar UD et al (2008) Efficacy of aloe vera gel in the treatment of vulval lichen planus. J Coll Physicians Surg Pak 18:612-614.
11. Simark-Mattsson C et al (2013) Reduced immune responses to purified protein derivative and Candida albicans in oral lichen planus. J Oral Pathol Med 42:691-697.
12. van der Meij EH et al.(2003) The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective study.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 96:164-171.