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Lichen sclerosus

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Lichen sclerosus
Other namesBalanitis xerotica obliterans, lichen sclerosus et atrophicus,[1] Lichen sclerosis et atrophicus,[2] lichen plan atrophique, lichen plan scléreux, Kartenblattförmige Sklerodermie, Weissflecken Dermatose, lichen albus, lichen planus sclerosus et atrophicus, dermatitis lichenoides chronica atrophicans, kraurosis vulvae[3]
Micrograph of lichen sclerosus showing the characteristic subepithelial sclerosus (right/bottom of image). H&E stain.
SpecialtyGynaecology

Lichen sclerosus (LS) is a chronic, inflammatory skin disease, of unknown cause, which can affect any body part of any person, but has a strong preference for the genitals (penis, vulva), and is also known as balanitis xerotica obliterans when it affects the penis. Lichen sclerosus is not contagious. There is a well-documented increase of skin cancer risk in LS, potentially improvable with treatment.[4][5] LS in adult age women is normally incurable, although treatment can lessen its effects, and it often gets progressively worse if not treated properly. Most males with mild or intermediate disease, restricted to foreskin or glans, can be cured by either medical or surgical treatment.[6]

Signs and symptoms

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Lichen sclerosus on an 82-year-old woman, showing an ivory white coloring in the vulva, and also stretching downward to the perineum.
Balanitis xerotica obliterans. 70 year old man.

LS can occur without symptoms. White patches on the LS body area, itching, pain, dyspareunia (in genital LS), easier bruising, cracking, tearing and peeling, as well as hyperkeratosis, are common symptoms in both men and women. In women, the condition most commonly occurs on the vulva and around the anus with ivory-white elevations that may be flat and glistening.[citation needed]

In males, the disease may take the form of whitish patches on the foreskin and its narrowing (preputial stenosis), forming an "indurated ring", which can make retraction more difficult or impossible (phimosis). In addition there can be lesions, white patches or reddening on the glans. In contrast to women, anal involvement is less frequent. Meatal stenosis, making it more difficult or even impossible to urinate, may also occur.[citation needed]

On the non-genital skin, the disease may manifest as porcelain-white spots with small visible plugs inside the orifices of hair follicles or sweat glands on the surface. Thinning of the skin may also occur.[7]

Psychological effect

[edit]

Distress due to the discomfort and pain of lichen sclerosus is normal, as are concerns with self-esteem and sex. Counseling can help.[citation needed]

According to the US National Vulvodynia Association, which also supports women with lichen sclerosus, vulvo-vaginal conditions can cause feelings of isolation, hopelessness, low self-image, and much more. Some women are unable to continue working or have sexual relations, and may be limited in other physical activities.[8][9] Depression, anxiety, and even anger are all normal responses to the ongoing pain LS sufferers experience.

Pathophysiology

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Although it is not clear what causes LS, several theories have been postulated. Lichen sclerosus is not contagious and cannot be caught from another person.[10]

Several risk factors have been proposed, including exposure to the irritant effects of urine, autoimmune diseases, infections and genetic predisposition.[11][12] There is evidence that LS can be associated with thyroid disease.[13]

Exposure to urine

[edit]

There is a growing body of evidence suggesting that prolonged exposure of susceptible tissues to the irritant effects of urine may contribute to the development of lichen sclerosus.[14][15][16]

Urine droplets that leak after urination can become trapped in the external genitalia (e.g., beneath the foreskin), creating an occluded environment that exacerbates irritation and inflammation.[17]

Several observations support the "urine occlusion hypothesis," including:

  • Rare incidence in circumcised individuals: Lichen sclerosus is extremely rare in individuals circumcised during childhood.[18]
  • Resolution through circumcision: In affected men, lichen sclerosus can be effectively treated or cured by circumcision.[19]
  • Recurrence with neo-foreskin formation: In circumcised men who later develop a neo-foreskin over time, the disease can reappear.[20]
  • Pattern of distribution: The typical distribution of lichen sclerosus corresponds to areas exposed to urine. In men, the condition is usually confined beneath the foreskin, while in women, it can involve the perianal region.[21][22][23]
  • Lichen sclerosus in urine-diverted sites: When urine is diverted to other areas of the body, the skin in those regions can also develop lichen sclerosus.[24][25]

Genetic

[edit]

Lichen sclerosus may have a genetic component. A high correlation of lichen sclerosus has been reported between twins[26][27] and between family members.[28]

Autoimmunity

[edit]

Autoimmunity is a process in which the body fails to recognize itself and therefore attacks its own cells and tissue. Specific antibodies have been found in LS sufferers. Furthermore, there seems to be a higher prevalence of other autoimmune diseases such as diabetes mellitus type 1, vitiligo, alopecia areata, and thyroid disease.[29][30]

Infection

[edit]

Both bacterial and viral pathogens have been implicated in the etiology of LS. A disease that is similar to LS, acrodermatitis chronica atrophicans is caused by the spirochete Borrelia burgdorferi. Viral involvement of HPV[31] and hepatitis C[32] are also suspected.

A link with Lyme disease is shown by the presence of Borrelia burgdorferi in LSA biopsy tissue.[33]

Hormones

[edit]

Since LS in females is primarily found in women with a low estrogen state (prepubertal and postmenopausal women), hormonal influences have been postulated. To date though, very little evidence has been found to support that theory.[citation needed]

Local skin changes

[edit]

Some findings suggest that LS can be initiated through scarring[34] or radiation,[35][36] although those findings were sporadic and very uncommon.[citation needed]

Diagnosis

[edit]
Micrograph of extragenital lichen sclerosus: epidermal atrophy, follicular plugging and basal vacuolization, and sclerosis with initial homogenization of collagen in the dermis.[37]

The disease often goes undiagnosed for several years, because it is sometimes not recognized, and misdiagnosed as thrush or other problems, and not correctly diagnosed until the patient is referred to a specialist after the problem does not clear up.[citation needed]

A biopsy of the affected skin can be done to confirm a diagnosis. When a biopsy is done, hyperkeratosis, atrophic epidermis, sclerosis of dermis and lymphocyte activity in dermis are histological findings associated with LS.[38] The biopsies are also checked for signs of dysplasia.[39]

It has been noted that clinical diagnosis of balanitis xerotica obliterans can be "almost unmistakable," though there are other dermatologic conditions such as lichen planus, localized scleroderma, leukoplakia, vitiligo, and the cutaneous rash of Lyme disease can have a similar appearance.[40]

Treatment

[edit]

Main treatment

[edit]

There is no definitive cure for LS.[41] Behavior change is part of treatment. The patient should minimize or, preferably, stop scratching LS-affected skin.[42] Any scratching, stress or damage to the skin can worsen the disease. Scratching has been theorized to increase cancer risks.[43] Furthermore, the patient should wear comfortable clothes and avoid tight clothing, as it is a major factor in the severity of symptoms in some cases.[43][44]

Corticosteroids applied topically to the LS-affected skin are the first-line treatment for lichen sclerosus in both women and men, with strong evidence showing that they are "safe and effective" when appropriately applied, even over long courses of treatment, rarely causing serious adverse effects.[45][46][47][48][49] They improve or suppress all symptoms for some time, with high variance across patients, until it is required to use them again.[50] Methylprednisolone aceponate has been used as a safe and effective corticosteroid for mild and moderate cases.[51] For severe cases, it has been theorized that mometasone furoate might be safer and more effective than clobetasol.[51] Recent studies have shown that topical calcineurin inhibitors such as tacrolimus can have an effect similar to corticosteroids, but its effects on cancer risks with LS are not conclusively known.[52][53] Based on limited evidence, a 2011 Cochrane review concluded that clobetasol propionate, mometasone furoate, and pimecrolimus (calcineurin inhibitor) all are effective therapies in treating genital lichen sclerosus.[54] However, randomized-controlled trials are needed to further identify the optimal potency and regimen of topical corticosteroids, and assess the duration of remission and/or the prevention of flares patients experience with these topical therapies.[54]

Continuous use of appropriate doses of topical corticosteroids is required to ensure symptoms remain relieved over the patient's life time. If continuously used, corticosteroids have been suggested to minimize the risk of cancer in various studies. In a prospective longitudinal cohort study of 507 women throughout six years, cancer occurred for 4.7% of patients who were only "partially compliant" with corticosteroid treatment, while it occurred in 0% of cases where they were "fully compliant".[55] In a second study, of 129 patients, cancer occurred in 11% of patients, none of whom were fully compliant with corticosteroid treatment.[51] Both those studies, however, also said that a corticosteroid as powerful as clobetasol is not necessary in most cases. In a prospective study of 83 patients, throughout 20 years, eight developed cancer. Six already had cancer at presentation and had not had treatment, while the other two were not taking corticosteroids often enough.[50] In all three studies, every single cancer case observed occurred in patients who were not taking corticosteroids as often as the study recommended.[citation needed]

Continuous, abundant usage of emollients topically applied to the LS-affected skin is recommended to improve symptoms. They can supplement, but not replace, corticosteroid therapy.[46][48][56] They can be used much more frequently than corticosteroids due to the extreme rarity of serious adverse effects. With genital LS, appropriate lubrication should always be used before and during sex in order to avoid pain and the worsening the disease.[57] Some oils, such as olive oil and coconut oil, can be used to accomplish both the emollient and sexual lubrication function.[citation needed]

In males, it has been reported that circumcision can have positive effects, but does not necessarily prevent further flare-ups of the disease[58] and does not protect against the possibility of cancer.[59] Circumcision does not prevent or cure LS. In fact, "balanitis xerotica obliterans" in men was first reported by Stühmer in 1928. as a condition affecting a set of circumcised men.[3]

Other treatments

[edit]

Carbon dioxide laser treatment is safe and effective, and improves symptoms over the long term,[60] but it does not lower cancer risks.

Platelet-rich plasma was reported to be effective in one study, producing large improvements in the patients' quality of life, with an average IGA improvement of 2.04 and DLQI improvement of 7.73.[61]

Prognosis

[edit]

The disease can last for a considerably long time. Occasionally, "spontaneous cure" may occur,[62] particularly in young girls.

Lichen sclerosus is associated with a higher risk of cancer.[63][64][65][66] Skin that has been scarred as a result of lichen sclerosus is more likely to develop skin cancer. Women with lichen sclerosus may develop vulvar carcinoma.[67][68] Lichen sclerosus is associated with from 3 to 7% of all cases of vulvar squamous cell carcinoma.[69] In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS.[70][71] A study in men noted that: "the reported incidence of penile carcinoma in patients with balanitis xerotica obliterans is 2.6–5.8%".[72]

Epidemiology

[edit]

There is a bimodal age distribution in the incidence of LS in women. It occurs in females with an average age of diagnosis of 7.6 years in girls and 60 years old in women. The average age of diagnosis in boys is from 9 to 11 years old.[73]

In men, the most common age of incidence is 21 to 30.[74]

History

[edit]

In 1875, Weir reported what was possible vulvar or oral LS was "ichthyosis." In 1885, Breisky described kraurosis vulvae. In 1887, Hallopeau described a series of extragenital cases of LS. In 1892, Darier formally described the classic histopathology of LS. In 1900, the concept was formed that scleroderma and LS were closely related, which continues to this day. In 1901, pediatric LS was described. From 1913 to present, the concept that scleroderma is not closely related to LS also was formed. In 1920, Taussig established vulvectomy as the treatment of choice for kraurosis vulvae, a premalignant condition. In 1927, Kyrle defined LS ("white spot disease") as an entity sui generis. In 1928, Stühmer described balanitis xerotica obliterans as a postcircumcision phenomenon. In 1936, retinoids (vitamin A) were used to treat LS. In 1945, testosterone was used in genital LS. In 1961, the use of corticosteroids started. Jeffcoate presented an argument against vulvectomy for simple LS. In 1971, progesterone was used in LS. Wallace defined clinical factors and the epidemiology of LS. In 1976, Friedrich defined LS as a dystrophic and not an atrophic condition, and "et atrophicus" was dropped. The International Society for Study of Vulvar Disease classification system established that "kraurosis" and "leukoplakia" were no longer to be used. In 1980, fluorinated and superpotent steroids were first used to treat LS. In 1981, studies into HLA serotypes and LS were published. In 1984, etretinate and acetretin were used in LS. In 1987, LS was linked with Borrelia infection.[3]

Lichen sclerosus et atrophicus was first described in 1887 by François Henri Hallopeau.[75] Since not all cases of lichen sclerosus exhibit atrophic tissue, the use of et atrophicus was dropped in 1976 by the International Society for the Study of Vulvovaginal Disease (ISSVD), officially proclaiming the name lichen sclerosus.[76]

See also

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References

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  4. ^ Kravvas, G.; Ge, L.; Ng, J.; Shim, T. N.; Doiron, P. R.; Watchorn, R.; Kentley, J.; Panou, E.; Dinneen, M.; Freeman, A.; Jameson, C.; Haider, A.; Francis, N.; Minhas, S.; Alnajjar, H. (March 2022). "The management of penile intraepithelial neoplasia (PeIN): clinical and histological features and treatment of 345 patients and a review of the literature". The Journal of Dermatological Treatment. 33 (2): 1047–1062. doi:10.1080/09546634.2020.1800574. ISSN 1471-1753. PMID 32705920.
  5. ^ Kravvas, G.; Shim, T.N.; Doiron, P.R.; Freeman, A.; Jameson, C.; Minhas, S.; Muneer, A.; Bunker, C.B. (2017-08-16). "The diagnosis and management of male genital lichen sclerosus: a retrospective review of 301 patients". Journal of the European Academy of Dermatology and Venereology. 32 (1): 91–95. doi:10.1111/jdv.14488. ISSN 0926-9959. PMID 28750140.
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Medical pictures

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