Lichen planus classic type L43.-

Erasmus Wilson, 1869

Non-contagious, subacute to chronic, markedly pruritic, usually self-limited (duration of disease between 1 month and 10 years), inflammatory disease of the skin and/or mucous membranes covered with squamous epithelium (intestinal mucosa and mucous membranes of the urogenital tract remain uninvolved) of unknown etiology, with typical clinical (papules shining on the skin as if polished) and histological morphology (destruction of basal keratinocytes by cytotoxic T cells) and a characteristic distribution pattern often accentuated on the flexor side.

Lichen planus is characterized by a characteristic "lichenoid tissue reaction", which can also occur in other inflammatory processes of the skin (e.g. in lichenoid drug reactions, in a "graft-versus-host reaction" in initial lichen sclerosus et atrophicus, in erythema dyschromicum perstans).

Prevalence: 0.2%-5.0% of the (adult) population with differences in the respective subtypes. The estimated incidence of LP in the general population is between 0.1% and 1.27%. Based on 100,000 people, the overall prevalence is 90.3 and the overall incidence is 20.6/100,000 (Schruf E et al. 2022).

In contrast, a very low prevalence and incidence were observed in adolescents and children.

Up to 25% of patients have isolated lichen planus of the mucosa.

Familial lichen planus is rare (about 100 cases are known). Earlier age of manifestation than in non-familial LP.

Autoimmune reaction: To date, the etiology and pathogenesis of lichen ruber is not fully understood. There are correlations with autoimmune diseases, viral infections, medications and mechanical trigger factors (scratching, rubbing, etc.). LP-like lesions occur in chronic graft-versus-host disease (GVHD ), in which alloreactive, cytotoxic T cells and antibodies that recognize foreign MHC molecules are decisive effectors. The morphological analogy of the dermatitic reactions leads to the hypothesis that in lichen planus there is an autoimmune reaction against epitopes of basal keratinocytes that have been modified by viral or drug induction. It is undisputed that the apoptotic destruction of the basal keratinocytes represents the common final stage of the lichen planus reaction (this certainly also plays an important role in other autoimmune skin diseases, e.g. LE). Ligand-receptor-dependent dysregulation(TNF-alpha/TNFR1= TNF-alpha receptor) is discussed as the cause. The direct "pore formation" by perforin and the subsequent enzymatic degradation by serine proteases (see granzyme B below), which is known to occur during apoptosis, is also discussed.

In early changes, the clear proliferation of antigen-presenting cells (APCs) is noticeable. These are possibly induced by the keratinocytes themselves through a dysregulation of cytokine production.

Viral antigens appear to play a preferential role in the aetiopathogenesis of lichen ruber. The prevalence of HCV/HBV infections (hepatitis C/B) is 13.5 times higher in lichen planus than in controls. In oral lichen planus, a high percentage of HCV RNA and TTV DNA (transfusion-transmitted virus) was detected in lesional mucosa. The occurrence of lichen ruber after HBV vaccine has been described. The etiopathogenetic significance of HHV-7/HHV-8 cannot be clearly proven. Noteworthy are reports of the occurrence of lichen ruber after SARS-CoV-2 vaccination (Zengarini C et al. 2022). The same can be reported for erythema multiforme

Drugs: Lichen ruber as ADR after therapy with monoclonal antibodies against programmed cell death 1 (anti-PD-1 - e.g. nivolumab): These ADRs include both classic lichen ruber and, in rarer cases, pemphigoid lichen ruber. Naproxen is known to be another lichen planus inducer (Güneş AT et al. 2006).

Diabetes mellitus: An association of lichen ruber and diabetes mellitus is strikingly common. Every 2nd patient has a disorder of glucose metabolism and every 4th has manifest diabetes mellitus.

Contact allergens: The role of contact allergies to a number of metal salts (gold, amalgam, copper) is well known in oral lichen ruber. It is discussed that these antigens can trigger an LP reaction in the manner of haptens.

Paraneoplasia: There are isolated reports of paraneoplastic lichen ruber.

Familial occurrence: about 100 cases of familial lichen planus have been reported so far. There is no significant relationship to specific HLA types.

Preferably occurring in adults in the 3rd to 6th decade of life. Rare in children (about 1-4% of cases).

No ethnic predisposition. Women seem to be affected slightly more often than men (see also Lichen planus mucosae).

Affected are:

Flexor side of the wrists and forearms, lateral ankle area of the ankles

Mucosal infestation (30-40%): penis, oral and genital mucosa, esophageal mucosa)

Nails (10%)

Capillitium (see also Graham-Little syndrome).

Generalized or universal (erythrodermic) occurrence is possible (see also Lichen planus exanthematicus)

Initially about 0.1 cm in size, surrounded by the natural skin furrows, raised, plateau-like, smooth, shiny like lacquer (surface smooth as if polished), clearly itchy, red papules. Aggregation of several papules with formation of plaques of different sizes. Small lamellar scaling is rarely visible.

The diagnostically important surface reflection of the lichen planus papules is best recognized when light falls on it from the side. Wickham's pattern and the linear arrangement of the efflorescences in scratching or rubbing marks are also typical (see Köbner phenomenon [= isomorphic stimulus effect] below). The lesional itching is responded to by the patient by rubbing ( shiny nails are often detectable); excoriations rarely occur (this means that fresh or older scratch erosions such as those to be expected in atopic dermatitis are absent).

Localized, rough, yellow-reddish, hyperkeratotic plaques appear on the palms and soles, including the lateral edges, with a red border at the edges.

A varying degree of oral mucosal infestation (see also Lichen planus mucosae) is observed in > 50% of patients. Typical are symmetrical, reticular or nummular white plaques, also disseminated, 0.1 cm large white papules of the buccal mucosa and/or the tongue and/or the gingiva. A special feature is the painful and therapy-resistant erosive lichen planus of the oral mucosa.

Genitalia, especially the glans penis and vulva, are often affected in the form of anular or circinate, whitish but also red or erosive plaques (see below Lichen ruber mucosae/ Lichen planus vulvae).

Capillitium (see below Lichen ruber follicularis capillitii).

Nails: Frequently thinned and shortened ("starvation halfway") nails, frequently frayed nail plates with longitudinal distortions of the surface and numerous spots. Pterygia possible. Rarely colorless or red longitudinal striations(erythronychia). Complete destruction of the nail plate is possible. It is not uncommon to find shiny nails (consequence of permanent chafing).

No pioneering laboratory parameters!

Uniform and pathognomic histologic pattern of a classic interface dermatitis with irregular, often sawtooth-like acanthosis, compact orthohyperkeratosis with prominent hypergranulosis (circumscribed thickening of the keratohyalin-containing cell layers of the stratum granulosum causes the clinical picture of Wickham's pattern). Usually very prominent, dense, band-shaped, lymphoid cellular, epidermotropic infiltrate. The inflammatory infiltrate consists predominantly of oligoclonal, CD8-positive, cytotoxic T cells. Focal pigment incontinence. Vacuolar degeneration of the basal epithelial cell layers, resulting in clefts (Max Joseph's spaces) and even subepithelial blistering (lichen planus bullosus). Detection of numerous cytoid bodies (Civatte bodies or cytoid bodies (colloid bodies), see below. apoptosis). Epidermal Langerhans cells are increased in active lesions. Plasma cells, neutrophil and eosinophil leukocytes may be present, but are not common.

Typical, strong, band-shaped subepithelial fibrin deposits. Clear spherical fluorescence phenomena due to the detection of several immunoglobulins, especially IgM, complement or fibrinogen, in connection with apoptotic keratinocytes (Civatte bodies). Linear immunoglobulin detection is rare. The DIF with a sensitivity of 75 % is particularly helpful in differentiating between erosive LP and immunobullous diseases such as pemphigus vulgaris.

• Clinical differential diagnoses:
  • Integument:
    • Psoriasis punctata: The Auspitz phenomenon is always detectable and always absent in lichen planus!
    • Lichenoid medicinal exanthema: History; usually no involvement of the oral mucosa.
    • Pityriasis lichenoides et varioliformis acuta: As in "Heubner's star chart" very polymorphous, pruritic or also burning exanthema, with papules, erosions, ulcers and possibly hemorrhagic vesicles. Lichen planus exanthema is monomorphic.
    • Papular syphilid: Clinically, the lichenoid character of the single-cell lesions is absent; pruritus is mild or absent.
    • Scabies: Multiple erythematous papules on the wrists may complicate the differential diagnosis of scabies and lichen ruber.
  • Oral mucosa:
    • Leukoplakia: In the area of the oral mucosa, leukoplakia or mechanical mucosal irritations have to be differentiated. Histological clarification is necessary. In both cases the typical "anular structures" of the LP are missing.
    • Candidiasis of the oral mucosa: Infestation of the tongue, cheek mucosa and soft and hard palate with white to grey-white plaques that can be easily wiped off (LP cannot be wiped off!).
    • Gingivitis marginalis: similar, therapy-resistant pattern with analogous symptoms. Histological clarification is necessary.
• Histological differential diagnoses:
  • Lichenoid medicinal exanthema: Largely identical picture, apoptotic keratinocytes are frequent, possibly focal parakeratosis, which is always absent in lichen planus. Marked histoeosinophilia is possible as well as a plasma cell infiltrate component.
  • Fixed drug reaction: Numerous apoptotic keratinocytes, perivascular infiltrate thickening, often marked eosinophilia, prominent pigment incontinence.
  • Lichensclerosus et atrophicus: Initial lichenoid infiltrate without 3-zone phenomenon. Pattern analogous to lichen planus; later typical zonal pattern.
  • Acute graft-versus-host disease: Numerous apoptotic keratinocytes, strong vacuolization of the junctional zone, less dense infiltrate.
  • Papular syphilid: Epidermis with psoriasiform acanthosis and focal spongiosis; admixture of neutrophilic granulocytes and (numerous) plasma cells.

There is a certain (unspecified) risk of developing epithelial tumors (spinocellular carcinomas) in long-term persistent LP lesions of the skin and mucous membranes. The risk of malignant changes in the lip or oral mucosa is 7 times higher in LP patients.

The diagnoses of alopecia areata and vitiligo are also significantly more common in LP patients than in control collectives (Schruf E et al. 2022).

In larger collectives, dyslipidemia and autoimmune thyroiditis occur more frequently than in a control group ( Schruf E et al. 2021).

The therapy depends on an identifiable cause (e.g. medication such as antihypertensives, NSAIDs), the clinical aspect (localized/generalized) and the previous course (acute/chronic). In many cases, the treatment of itching is the main focus.

Glucocorticoids (currently parkatized first-line standard): For circumscribed asymptomatic findings, medium-strength glucocorticoids such as 0.25% prednicarbate (e.g. ^Dermatop® cream), 0.1% mometasone furoate (e.g. Ecural® fat cream), in persistent cases also strong 0.05% glucocorticoids such as clobetasol (e.g. ^Dermoxin® cream), if necessary also under occlusion (2 times/day 2-4 hours).

If necessary, inject the foci with glucocorticoid crystal suspension such as triamcinolone acetonide (e.g. ^Volon® A) 10-40 mg with 2-4 ml 1% mepivacaine in a syringe and apply intrafocally.

Calcineurin inhibitors: Tacrolimus or Pimecrolimus can be used topically as off-label use. Both substances are particularly effective in cases of mucosal infestation. However, due to the unknown long-term effects of calcineurin inhibitors and the carcinogenicity of pimecrolimus proven in animal experiments, the indication for treatment with calcineurin inhibitors must be extremely strict!

PUVA: For extensive, especially disseminated forms, PUVA bath therapy, a re-PUVA therapy (PUVA + Acitretin) or a systemic PUVA therapy are suitable. Success is shown in approx. 80-90% of cases.

Acitretin: In the case of extensive infestation, start treatment with acitretin (neotigason) initially 0.5 mg/kg bw/day, maintenance dose 0.1-0.2 mg/kg bw/day according to the clinic. Systemic retinoids achieve the highest levels of evidence in studies (Schilling L et al. 2018). Discontinuation trial after 1/2 year at the earliest.

Alternatively or in severe cases: acitretin in combination with glucocorticoids such as prednisolone (e.g. Decortin H) initially 0.5 mg/kg bw/day, tapering over a period of 4-6 weeks. Maintenance dose according to clinic with 5-10 mg/day.

Alternatively: Other systemic therapeutic agents that have been described in various smaller studies can be regarded as "third line" therapy for therapy-resistant lichen planus of the external integument. These include: Ciclosporin A, griseofulvin, oral metronidazole, sulfasalazine, mycophenolate mofetil, azathioprine, thalidomide.

Alternative, experimental: Apremilast, an oral thalidomide analog that has been successfully tested in a small monocentric study for exanthematic lichen planus.

Still in clinical trials are 1L-17A inhibitors, JAK1/2 inhibitors and OSMRbeta inhibitors.

Special issues:

• In cases of therapy-resistant lichen planus erosivus mucosae (see there), stronger local or systemic immunosuppressive measures are necessary.
• Lichen planus genitalis: Therapeutic measures see below. Lichen planus erosivus mucosae.
• Lichen planus follicularis capillitii (see there).
• Lichen planus of the nails: I.A. no special therapy, as nail changes usually occur with other LP lesions. Some US authors recommend perilesional injections with glucocorticoids(caution! painfulness). In individual cases, good therapeutic success has been reported with Ciclosporin A (initial: 2x100mg/day p.o. maintenance dose 100mg/day p.o.). Own experience exists with azathioprine (initial: 1.0-1.5mg/kgKG, maintenance dose at 0.5mg/kgKG).
• In the case of drug-induced lichen planus, the initiating medication should be discontinued. Otherwise treatment as for classic lichen planus.

Classic cutaneous LP is self-limiting and usually heals within 6 (>50%) to 18 months (85%). However, chronic courses lasting for years (decades) are also possible. Mucosal changes that persist for years are to be regarded as facultative precancerous lesions!

Externally: Phytotherapy: Anti-itching plant ingredients with cooling effect such as: camphor, mint or peppermint oil, menthol in DAC cream as a base, capsaicin (0.02-0.075%) can be applied on intact skin! 2-3x /day can be applied.

Formulation example for a 1% menthol cream:

• Menthol1,0
• DAC base cream ad 100,0.
• S.:Apply Ambiphilic 1% Menthol Cream 2-3 times/day to itchy skin areas. Use-by date: Tube: 6 months

Systemic: Oral bromelain (e.g. Bromelain-POS) or Phlogenzym(Phlogenzym-mono) is further recommended.

Patients with lichen planus are primarily treated by dermatologists and general practitioners, followed by gynecologists and internists.

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