Lichen sclerosus (overview) L90.4

Lichen sclerosus (lichen from Greek leichen = lichen, sclerosus from Greek skleros = hard, dry, brittle) is an acquired, non-infectious, mucocutaneous, chronic inflammatory (autoimmunological) disease with a phasic course.

Clinical-topographical the Lichen sclerosus can be classified:

• Lichen sclerosus of the penis (male)
• Lichen sclerosus of the vulva (of the woman)
• Extragenital lichen sclerosus

The different clinical processes and prognoses allow a classification into:

• Prepubertal lichen sclerosus
• Postpubertal lichen sclerosus

Different information depending on the collective.

Prevalences of 0.1% are reported for young girls and up to 3% for adult women.

Cross-sectional analyses of larger non-preselected male US collectives showed prevalences of 1.4 - 2.1/100,000.

It is (analogous to lichen planus) a T-cell-mediated disease (Terlou A et al. 2012)

An autoimmunological genesis is discussed; furthermore, hormonal factors, dysregulation of the sex hormones, infectious genesis(Borrelia burgdorferi; EBV infection ?), formation of autoantibodies against ECM1 (extracellular matrix protein-1 - detection in 60-70% of cases; the occurrence of these autoantibodies appears to be more of a secondary phenomenon), genetic disposition (rare familial occurrence, association with HLA-B40, HLA-B44). Specific autoantibodies are absent. Hyaluronic acid is accumulated in the lichen sclerosus lesion, associated with reduced expression of CD44 (Kaya G et al. (2000).

Evidence of associated autoimmune diseases such as (figures from a collective of 190 patients):

• autoimmunological thyroid diseases (16%)
• Vitiligo (10%)
• alopecia areata (3%)
• pernicious anemia (3%)
• primary biliary cirrhosis

An association with systemic lupus erythematosus was mentioned in several case reports.

Immunohistological similarities with circumscribed scleroderma suggest a possible pathogenetic relationship.

The genital lichen sclerosus shows 2 age peaks:

• Prepubertal: Start in children mostly between 5-11 years of age.
• Postpubertal: Adult women and men are affected in middle age (30-50 years), women preferably in menopause; possibly the first symptoms appear already well before menopause (Kirtschig G 2018).

Women are affected 4-10 times more frequently than men.

The extragenital lichen sclerosus mainly affects adults. About 6-11% of the entire lichen sclerosus collective is affected extragenitally.

Genitoanal area: vulva, prepuce, glans penis, anal area (often genito-anal pattern in an 8-formation, this is mainly detectable in prepubertal lichen sclerosus).

Extragenital (about 10% of cases): Mainly lateral neck area, clavicle area, presternal, submammary also mammary, flexor sides of forearms, shoulders, rarely oral mucosa.

I. Genital/genito-anal lichen sclerosus:

• Prepubertal: Anogenital involvement is typical, with sharply demarcated, whitish plaques with a mirror-like surface, often involving the vulva and anus in an 8-formation. The initial foci of lichen sclerosus usually cause no discomfort. Mild pruritus is occasionally reported,
• In adults, excruciating pruritus, sometimes combined with pain (rhagaden formation), is most prominent, especially during sexual intercourse.
• In the later course, whitish atrophic, porcelain-like plaques with a marked increase in consistency are found with a tendency to shrink. Frequently bleeding rhagades with a tendency to superinfection. Furthermore, also extensive, long-term persistent lesional hemorrhages, which can dominate the clinical picture and be diagnostically irritating (sclerosis is covered by older or fresh "blood lakes"). In the late stage, different degrees of vulvar atrophy with atrophy of the small labia (small labia may disappear completely) and subsequently of the large labia, in the further late stage findings of Kraurosis vulvae.
• Men (see below Lichen sclerosus of the penis): Balanopreputial sclerosis with erosions and rhagades. Also planar haemorrhages, and varying severity of phimosis. Synechiae; in the late stage picture of the so-called "Balanitis xerotica obliterans". The concordant development of squamous cell carcinoma is about 5% in larger collectives.

II. extragenital lichen sclerosus:

1. Confetti type: There are usually disseminated or grouped, white or gray-brown, about 0.2-0.5 cm large spots and plaques. Occur mainly on the axillae and flexor sides of the wrists, on the trunk and neck. In this type there is often no mucosal involvement.
2. Map type: In this type, the initially small foci of lichen sclerosus are confluent into larger,map-like areas of patches and plaques with atrophic parchment-like surfaces (often affecting the female mammae). Red borders around the foci are typical (sign of underlying inflammation). Band-like hyperpigmentation is also found in the margins of lichen sclerosus. Less common is lesional blistering. Almost pathognomonic are lesional hemorrhages, which can be found in different shades of red (light red, deep red or reddish brown) depending on the duration of the condition. Involvement of the oral mucosa is very rare.
3. Special forms: Bullous or hemorrhagic lichen sclerosus. The hemorrhagic component results from secondary (often trauma-induced) hemorrhage into the area of lichen sclerosus. In this "bradytrophic" zone, blood is broken down only very slowly, so that the hemorrhage is detectable for several weeks.

Early stage: epithelial atrophy, orthohyperkeratosis, hypergranulosis. Subepithelial band-like arranged, epidermotropic round cell infiltrate. The density of this infiltrate may be considerable, so that a differential diagnosis must be made to differentiate it from epidermotropic cutaneous T-cell lymphomas.

Intermediate stage: Edema zone free of elastic fibers, with wide gaping blood and lymphatic vessels, which pushes itself zipper-like between the epidermis and the band-like inflammatory zone. Bullous transformation is possible.

Late stage: Increasing sclerosing tendency and regression of cellular inflammatory phenomena.

Immunohistology: Dermal infiltrate predominantly of T lymphocytes, with high percentage of B lymphocytes (20-30%).

Note: sufficiently deep punch biopsy (do not squeeze) from lesional, non-steroidal pre-treated skin/mucosa.

Clinical:

• Circumscribed scleroderma (guttata type): no genital or anal involvement. Plaque-like on trunk and extremities. Surface not parchment-like rippling.
• Lichen planus: uniform livid color, usually clearly palpable elevations (papule or plaque); itching.
• Lichen simplex chronicus Vidal: no mucosal involvement, marked pruritus, extragenital cutaneous lesions
• Psoriasis anogenitalis: no mucosal involvement; sharp border to healthy skin; frequent extragenital involvement.
• Vitiligo: sharp, often bizarre demarcation to healthy skin; no itching, no induration of skin, extragenital involvement!
• Candida infections: macerated, blurred areas, inguinal and anal regions usually also affected. Obesity, immobility, immune disorders, mycological evidence of the yeasts!

Histological:

• Lichen ruber: hyperorthokeratosis, pronounced hypergranulosis, no formation of a so-called barren zone.
• Acrodermatitis chronica atrophicans: rather sparse diffuse lymphocytic infiltrate; relvanter proportion of plasma cells. No subepithelial band-like arrangement.
• Mycosis fungoides: dense lymphocytic infiltrate, cell and nuclear polymorphism, eosinophilic granulocytes. No barren zone.

Phimosis with subsequent complications; atrophy of the external genitals, Kraurosis vulvae (see also Lichen sclerosus of the vulva)

Remember! The lichen sclerosus et atrophicus in the genital area leads to the development of carcinoma in 3-6% of late adults. Women are preferentially affected!

It is important to define the therapy goal together with the patient. The focus is on minimizing the symptoms.

The therapeutic option to be chosen depends on the age of the patient, the localization (vulvar LS requires a different therapy than penile LS) and the severity of the disease (see below Lichen sclerosus of the vulva).

In cases of minor infestation (smaller plaques), purely local measures are preferable.

In more extensive cases of penile lichen sclerosus, an invasive procedure (circumcision) is recommended at an early stage.

Consistent external treatment is necessary, especially in the genital area, because of the excruciating itching and the progressive sclerosis.

• Glucocorticoids:
  • Glucocorticoids are the therapeutic agents of first choice (for procedure in vulvar lichen sclerosus see there). Intermittent shock therapy with the use of highly potent glucocorticoids is recommended.
  • Relatively good results can be achieved with intralesional glucocorticoid injections, such as triamcinolone acetonide crystal suspension (e.g. Triam 10 Lichtenstein burns less than Volon A) diluted 1:1 with local anesthetic, e.g. Scandicaine, especially in genital lesions with severe itching or pain. Injections can be used in combination with cryosurgery if necessary.
• Calcineurin inhibitors: Good clinical results with marked improvement of subjective symptoms and prolonged remissions can be obtained with topical therapy with tacrolimus (0.1% Protopic ointment) or pimecrolimus (Elidel cream 1%). Caution: inital burning sensation after application is often reported. Long-term experience is still lacking. In a transitional phase, it may be advisable to use the preparations in daily alternation with glucocorticoid externals.
• Hormones: In early stages in women, especially in younger women, therapy with estrogen- and progesterone-containing preparations (e.g. Linoladiol N cream, Cordes Estriol cream, Estriol ointment) for several weeks. Relatively good results are achieved with these products.
• In men, 2-5% testosterone ointment/gel (e.g. Androderm, R249 ) over several months often produces good results. This therapy should no longer be used for women because of the risk of virilization! Caution! Resorption! In girls this therapy is absolutely contraindicated!
• Careful external care: In case of infestation of the large or small labia, careful local care (dexpanthenol ointment R065, estrogen-containing hydrophilic creams) and meticulous intimate care. Use of a bidet after visiting the toilet, if bidet is not available, a good option would be the HappyPo Easy-Bidet (mobile hand-bottom shower). If this is not possible, first dab with damp toilet paper, then dab the lesions with oil-soaked hygienic wipes. Before sports or longer walks, apply a hydrophilic or hydrophobic ointment, e.g. Vaselin. alb. or Deumavan® ointment as a ready-to-use preparation.
• In addition, regular sitz baths with astringent agents (e.g. Tannosynt) are recommended for genital and perianal LS.
• Treatment of genital fluorosis, especially candidiasis.
• Alternative: Comparable results to calcineurin inhibitors, have been reported in an alternative approach using a thymus peptide active (Sclero Discret Thymusskin Intimate Care Cream). These results require further confirmation.

• in case of severe infestation, treatment with methotrexate (15mg/week over a period of 6-12 months; personal experience).
• Trial with acitretin (neotigason) 0.1-0.2 mg/kg bw/day (personal experiences are rather negative)
• Alternatively penicillin 10 Mega IU/day for 10 days, 3 treatment cycles at intervals of 4 weeks (therapy successes are not very satisfying!).
• Alternatively sulfasalazine (e.g. azulfidine) 2-4 g/day.
• If necessary, therapy with chloroquine (e.g. Resochin) 250 mg/day p.o. (this therapy strategy is also not very successful according to own experience!)

Surgical procedures should be used if the clinical symptoms are extensive:

• Cryosurgery: Good results can be achieved with the open procedure, in the case of circumscribed lesions with closed systems (stamps). Among these, there is a continuous improvement of itching and sclerosis (especially in the genital area). This therapy can also be used in children.
• Successes with ablative lasers have been reported. The long-term results remain to be seen.
• Circumcision is recommended in the case of prepuce and/or glans penis infections. Circumcision should be attempted at an early stage, as this therapy approach achieves the best long-term results.
• In case of lichen sclerosus of the vulva, surgical therapies are indicated if synechia and fusion of the labia have occurred. Surgical correction is also necessary in cases of constriction of the orifice externum of the urethra.

Quoad vitam good, quoad sanationem at first manifestation in adulthood doubtful. Chronic, possibly decades-long, intermittent course.

Irreversible atrophy of the genitals with phimosis and atrophy of the glans penis in men and so-called Kraurosis vulvae in women.

In the case of infantile lichen sclerosus, the chance of healing by puberty is > 80% (own observations!). However, in a small part of cases the changes persist (mostly in a lighter form) even in adulthood.

There is a clear association between genital lichen sclerosus and circumscribed scleroderma.

Note: Patients with genital lichen sclerosus often suffer from the "no man's land phenomenon". They find themselves on the borderline between dermatology and gynecology and do not feel that they are in good hands.

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4. Haefner HK et al (2014) The impact of vulvar lichen sclerosus on sexual dysfunction. J Womens Health (Larchmt) 23:765-770.

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6. Kaya G et al. (2000) Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus. J Invest Dermatol. 2000 Dec;115(6):1054-8.

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11. Lee H et al (2014) Segmental vitiligo and extragenital lichen sclerosus et atrophicus simultaneously occurring on the opposite sides of the abdomen. Ann Dermatol 26:764-765

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15. Patel B et al.(2015) Extra genital lichen sclerosus et atrophicus with cutaneous distribution and morphology simulating lichen planus. Indian J Dermatol 60:105

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19. Terlou A et al (2012) An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1
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