Lichen planus (overview) L43.-

Ferdinand v. Hebra 1860; Ernest Pierre Antoine Bazin 1862; Erasmus Wilson, 1869.

S.a. Newsletter"Lichen ruber

Non-contagious, acute, subacute to chronic, markedly pruritic, self-limited (duration of disease between 1 month and 10 years), (autoimmunological) inflammatory disease of the skin and/or mucous membranes of unknown etiology, with typical clinical (like polished shiny papules) and histological morphology (destruction of basal keratinocytes by cytotoxic T cells, lichenoid inflammation) and a characteristic, often flexor accentuated distribution pattern.

Lichen ruber (planus) is marked by a characteristic "lichenoid tissue reaction", which can also characterize the histological picture in other inflammatory processes of the skin, e.g. in lichenoid drug reactions, in a"graft-versus-host reaction" in initial lichen sclerosus, in lupus erythematosus, in erythema dyschromicum perstans or in actinic keratoses and is therefore characteristic but not specific for lichen ruber.

Depending on the clinical morphology and distribution pattern, lichen planus can be classified as follows:

Classification by distribution pattern:

1. Lichen planus exanthematicus (generalized lichen planus).
2. Localized lichen planus
3. Erythrodermic lichen planus
4. Lichen planus linearis (lichen ruber striatus)
   • Blaschkoid lichen planus(cutaneous mosaic)
   • Zosteriform lichen planus
5. Inverse lichen planus (see below Lichen planus pigmentosus inversus)
6. Lichen ruber mucosae/Orallichen planus
7. Lichen ruber genitalis (see also Lichen planus vulvae)
8. Lichen planus palmoplantaris
9. Lichen planusof the nails (nail lichen)

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Classification according to clinical appearance:

1. Lichen planus classic type
2. Lichen planus actinicus
3. Lichen planus anularis
4. Lichen planusverrucosus (hypertrophicus/obtusus)
5. Lichenplanus follicularis
6. Graham-Little syndrome
7. Lichen planus atrophicans
8. Lichen planuserosivus (erosive lichen planus)
9. Lichen planus pigmentosus
10. Lichen planus bullosus
11. Lichenplanus pemphigoides (considered a coincidental disease entity (overlap of lichen planus and bullous pemphigoid).
12. Lichen planus erythemato-squamosus (Lichen plan érythémato-squameux).
13. Invisible lichen planus (lichen invisible-Gougerot 1925) pruritic without definite clinical signs of LP; ehenmals lichen discretus). Entity is disputed.
14. Overlap Syndrome:
    • Lichen planus bullosus/pemphigoides
    • Lichen planus erythematosus/systemic lupus erythematosus.

Prevalence: 0.6%-1.2% of the (adult) population.

Up to 25% of patients have isolated lichen planus of the mucosa (see below Lichen planus mucosae).

Familial lichen planus is rare. About 100 cases are documented.

To date, the etiology and pathogenesis of lichen planus (LP) is not fully understood. This is all the more astonishing as the disease has been distinctly described since 1869 (Wilson). Significant relationships to a specific HLA phenotype have not been demonstrated. There are few sharply defined correlations to autoimmune diseases, to viral infections, to medications (see Lichen ruber e medicatione) as well as to mechanical trigger factors (scratching, rubbing, etc. may lead to isomorphism; see also Köbner phenomenon). Lichen ruber-like lesions occur in chronic graft-versus-host disease (GVHD), in which alloreactive cytotoxic T cells and antibodies recognizing foreign MHC molecules are crucial effectors. Familial lichen ruber is well known, although very rare.

The morphologic pathogenesis is also not fully understood (Vogt T (2018). The morphologic analogy of lichenoid dermatitic reactions led to the hypothesis that in lichen ruber there is an autoimmune reaction against epitopes of basal keratinocytes modified or induced by viral or drug induction. A striking feature is the marked proliferation of antigen-presenting cells (APZs), essentially Langerhans cells, which are detectable in early lesions of lichen ruber. The APZs may be attracted by the keratinocytes themselves, possibly via defective cytokine production. Ultimately, the nature of the autoantigens remains unclear to date. The antigen-presenting cells activate autoreactive T cells that produce further proinflammatory cytokines. Here, the Th1 cytokine interferon-gamma appears to play a key role.

It is undisputed that apoptotic destruction of basal keratinocytes is the common final pathway of the lichen-ruber reaction. Ligand-receptor-dependent dysregulation (TNF-alpha/TNFR1 = TNF-alpha receptor) is discussed as its cause. Keratinocytes eventually perish due to an interaction of FasL, the activating ligand of the Fas receptor, and Fas. Furthermore, membrane-damaging perforins are expressed, causing direct "pore formation" in the cell membrane with subsequent release of enzymatically acting serine proteases (see below Granzyme B) from the T cells. This cytotoxic activity explains vacuolization, pigment incontinence (loss of melanin to the dermis), apoptotic kamino bodies as morphological phenomena of the lichenoid reaction.

Other etiopathogentic associations:

• Unresolved is the question why, in contrast to the graft-versus-host reaction, only skin and mucous membranes are affected in lichen planus, the systemic involvement that characterizes GvHD is absent. An epidermis-specific, so far unknown autoantigen is postulated. This is also supported by the initiation of lichenoid inflammation by mechanical triggering. This is also supported by the fact that lichen ruber is only expressed on squamous epithelium (skin, mucous membranes near the skin, esophagus).
• Viral antigens appear to play an additive role in the etiopathogenesis of lichen planus. The prevalence of HCV/HBV infection (hepatitis C/B) is 13.5-fold higher in lichen ruber than in controls. In oral lichen planus, HCV RNA and transfusion-transmitted virus (TTV) DNA have been detected in a high percentage in lesional mucosa (see also Powell FC 1983).
• Vaccinations and lichen planus: The occurrence of lichen planus after HBV vaccination has been described. It is postulated that virally altered hepatocyte antigens express epitopes with homologies to keratinocyte antigens and thus activate autoreactive cytotoxic T cells. The occurrence of lichen planus after SARS-CoV-2 vaccination has been described several times (Zengarini C et al. 2022). In contrast to this, the etiopathogenetic significance of lichen planus to HHV-7/HHV-8 is not clearly provable.
• Diabetes mellitus: A strikingly frequent association is that of lichen planus and diabetes mellitus. One in 2 patients has a disorder of glucose metabolism and one in 4 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 planus. Here, it is discussed that these hapten-type antigens may trigger a lichen planus reaction.
• Drugs: Drug triggers include beta-receptor blockers, interferons, chloroquine, and nonsteroidal anti-inflammatory drugs.
• Paraneoplasia: Isolated reports of paraneoplastic lichen planus exist. An association with thymomas has been described (see Good syndrome below).

Preferably occurring in adults between the 3rd and 6th decade of life, rarely in children (about 1-4% of cases). No ethnic predisposition. Women seem to contract the disease slightly more frequently than men (Schilling et al. 2018).

Preferably, lichen ruber is found on the mucous membranes (65%), often on the skin and mucous membranes (20%), and less frequently isolated on the skin (10%).

Involvement of the nails and hair may result in permanent nail dystrophy or scarring irreversible alopecia.

Specifically, the following nail changes are described (cited in H. Hamm et al. 2018):

• Thinned nail plate
• Longitudinal furrows
• Onychorrhexis
• Dimples
• Rarer:
  • Onychoschisis
  • Trachyonychia
  • Onchyoatrophy
  • Koilonychia
  • Onycholysis
  • Onychomadesis
  • Reddening of the lunulae
  • Longitudinal melanonychia
  • Complete atrophy and scarring of the nail organ
  • Dorsal pterygium
  • Anonychia

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2. Brănişteanu DE et al. (2014) Cutaneous manifestations associated with thyroid disease. Rev Med Chir Soc Med Nat Iasi 118: 953-958.
3. Butch F et al (2014) Successful therapy of lichen planus of the nails nit ciclosporin. JDDG 12: 724-725
4. Chiheb S et al (2015) Clinical characteristics of naillichen planus and follow-up: A descriptive study of 20 patients. Ann DermatolVenereol 142:21-25
5. Deen K et al (2015) Mycophenolate mofetil in erosive genital lichen planus: A case and review of the literature. J Dermatol doi: 10.1111/1346-8138.12763
6. De Vries et al (2007) Lichen planus remission is associated with decrease of human herpes virus zype 7 protein expression in plasmacytoid dendritic cells. Arch Dermatol Res 299: 213-219
7. Eisman S, Orteu CH (2004) Recalcitrant erosive flexural lichen planus: successful treatment with a combination of thalidomide and 0.1% tacrolimus ointment. Clin Exp Dermatol 29: 268-270
8. Frieling U et al (2003) Treatment of severe lichen planus with mycophenolate mofetil. J Am Acad Dermatol 49: 1063-1066.
9. Gandolfo S et al (2004) Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population. Oral Oncol 40: 77-83
10. Hamm H et al (2018) Diseases of the nails. In: Braun-Falco`s Dermatology, Venereology Allergology G. Plewig et al. (eds) Springer Verlag p 1400.
11. Harden D et al (2003) Lichen planus associated with hepatitis C virus: no viral transcripts are found in the lichen planus, and effective therapy for hepatitis C virus does not clear lichen planus. J Am Acad Dermatol 49: 847-852.
12. Hodgson TA et al (2003) Long-term efficacy and safety of topical tacrolimus in the management of ulcerative/erosive oral lichen planus. Eur J Dermatol 13: 466-470.
13. Kraft K (2014) Naturally against pruritus. Hautnah Dermatology 30: 42-43.
14. Kolb-Maurer A et al (2003) Treatment of lichen planus pemphigoides with acitretin and pulsed corticosteroids. Dermatologist 54: 268-273
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17. Powell FC et al (1983) Primary biliary cirrhosis and lichen planus. J Am Acad Dermatol. 9:540-545.
18. Schilling L et al (2018) Lichen ruber planus. Dermatol 69: 100-108
19. Wilson E (1869) On lichen planus. J Cutan Med 8: 117
20. Wolf R et al (2010) Pleomorphism of lichen ruber - clinical variation, pathogenesis, and therapy. Act Dermatol 36: 180-185
21. Zengarini C et al (2022) Lichen ruber planus occurring after SARS-CoV-2 vaccination. Dermatol Ther 35:e15389.