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 (BXO) 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. LS in adult age women is normally incurable, but improvable with treatment, and often gets progressively worse if not treated properly. Most males with mild or intermediate disease restricted to prepuce or glans can be cured by either medical or surgical treatment.

Signs and symptoms

LS can occur without symptoms. White patches on the LS body area, itching, pain,

dyspareunia Dyspareunia ( ) is painful sexual intercourse due to medical or psychological causes. The term ''dyspareunia'' covers both female dyspareunia and male dyspareunia, but many discussions that use the term without further specification concern the ...

(in genital LS), easier bruising, cracking, tearing and peeling, and hyperkeratosis are common symptoms in both men and women. In women, the condition most commonly occurs on the

vulva The vulva (plural: vulvas or vulvae; derived from Latin for wrapper or covering) consists of the external female sex organs. The vulva includes the mons pubis (or mons veneris), labia majora, labia minora, clitoris, vestibular bulbs, vulv ...

and around the

anus The anus (Latin, 'ring' or 'circle') is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, the residual semi-solid waste that remains after food digestion, which, ...

with ivory-white elevations that may be flat and glistening. 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 Phimosis (from Greek φίμωσις ''phimōsis'' 'muzzling'.) is a condition in which the foreskin of the penis cannot stretch to allow it to be pulled back past the glans. A balloon-like swelling under the foreskin may occur with urination. In ...

). In addition there can be lesions, white patches or reddening on the glans. In contrast to women, anal involvement is less frequent.

Meatal stenosis Urethral meatal stenosis is a narrowing ( stenosis) of the opening of the urethra at the external meatus , thus constricting the opening through which urine leaves the body from the urinary bladder. Symptoms and signs * Abnormal strength and ...

, making it more difficult or even impossible to urinate, may also occur. On the non-genital skin, the disease may manifest as porcelain-white spots with small visible plugs inside the orifices of

hair follicles The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between ...

sweat glands Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial sur ...

on the surface. Thinning of the skin may also occur.

Psychological effect

Distress due to the discomfort and pain of lichen sclerosus is normal, as are concerns with self-esteem and sex. Counseling can help. According to the 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. Depression, anxiety, and even anger are all normal responses to the ongoing pain LS patients experience.

Pathophysiology

Although it is not clear what causes LS, several theories have been postulated. Lichen sclerosus is not contagious; it cannot be caught from another person. Several risk factors have been proposed, including

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

s and

genetic predisposition A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibili ...

. There is evidence that LS can be associated with

thyroid disease Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning ...

Genetic

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

Autoimmunity

Autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

is a process in which the body fails to recognize itself and therefore attacks its own cells and tissue. Specific

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...

have been found in LS. Furthermore, there seems to be a higher

prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

of other autoimmune diseases such as

diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

alopecia areata Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are pos ...

, and thyroid disease.

Infection

Both

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

l as well as viral pathogens have been implicated in the etiology of LS. A disease that is similar to LS,

acrodermatitis chronica atrophicans Acrodermatitis chronica atrophicans (ACA) is a skin rash indicative of the third or late stage of European Lyme borreliosis. ACA is a dermatological condition that takes a chronically progressive course and finally leads to a widespread atroph ...

is caused by the

spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

Borrelia burgdorferi ''Borrelia burgdorferi'' is a bacterial species of the spirochete class in the genus '' Borrelia'', and is one of the causative agents of Lyme disease in humans. Along with a few similar genospecies, some of which also cause Lyme disease, it mak ...

''. Viral involvement of

HPV Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

and

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...

are also suspected. A link with

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...

is shown by the presence of ''Borrelia burgdorferi'' in LSA biopsy tissue.

Hormones

Since LS in females is primarily found in women with a low

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

state (prepubertal and postmenopausal women), hormonal influences were postulated. To date though, very little evidence has been found to support this theory.

Local skin changes

Some findings suggest that LS can be initiated through scarring or radiation, although these findings were sporadic and very uncommon.

Diagnosis

The disease often goes undiagnosed for several years, as it is sometimes not recognized and misdiagnosed as

thrush ''The Man from U.N.C.L.E.'' is an American spy fiction television series produced by Metro-Goldwyn-Mayer Television and first broadcast on NBC. The series follows secret agents, played by Robert Vaughn and David McCallum, who work for a secret ...

or other problems and not correctly diagnosed until the patient is referred to a specialist when the problem does not clear up. A biopsy of the affected skin can be done to confirm diagnosis. When a biopsy is done,

hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologi ...

, atrophic epidermis, sclerosis of

dermis The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided ...

and

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic a ...

activity in dermis are histological findings associated with LS. The biopsies are also checked for signs of

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs ( macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopi ...

. It has been noted that clinical diagnosis of BXO can be "almost unmistakable," though there are other dermatologic conditions such as

lichen planus Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, and is only named that because it looks like one. It is characterized by polygonal, fla ...

, localized

scleroderma Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas ...

leukoplakia Oral leukoplakia is a ''potentially malignant disorder'' affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque th ...

, and the cutaneous rash of

can have a similar appearance.

Treatment

Main treatment

There is no definitive cure for LS. Behavior change is part of treatment. The patient should minimize or preferably stop scratching LS-affected skin. Any scratching, stress or damage to the skin can worsen the disease. Scratching has been theorized to increase cancer risks. 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. Topically applied corticosteroids to the LS-affected skin are the first-line treatment for lichen sclerosus in 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. They improve or suppress all symptoms for some time, which highly varies across patients, until it is required to use them again.

Methylprednisolone aceponate Methylprednisolone aceponate, or methylprednisolone acetate propionate, sold under the brand names Advantan and Avancort, is a glucocorticoid and a corticosteroid ester—specifically the C17α propionate and C21 acetate diester of methylpredn ...

has been used as a safe and effective corticosteroid for mild and moderate cases. For severe cases, it has been theorized that mometasone furoate might be safer and more effective than clobetasol. Recent studies have shown that topical

calcineurin inhibitor Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...

s such as tacrolimus can have an effect similar to corticosteroids, but its effects on cancer risks in LS are not conclusively known. Based on limited evidence, a 2011 Cochrane review concluded that clobetasol propionate, mometasone furoate, and

pimecrolimus Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis (however, Galderma has been promoting the compound i ...

(calcineurin inhibitor) all are effective therapies in treating genital lichen sclerosus. 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. Continuous usage of appropriate doses of topical corticosteroids is required to ensure symptoms stay 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 6 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". In a second study, of 129 patients, cancer occurred in 11% of patients, none of which were fully compliant with corticosteroid treatment. Both these 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, 8 patients developed cancer. 6 already had cancer at presentation and had not had treatment, while the other 2 were not taking corticosteroids often enough. In all three studies, every single cancer case observed occurred in patients who weren't taking corticosteroids as often as the study recommended. 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. They can be used much more frequently than corticosteroids due to the extreme rarity of serious adverse effects. Appropriate lubrication should be used every time before and during sex in genital LS in order to avoid pain and worsening the disease. Some oils such as olive oil and coconut oil can be used to accomplish both the emollient and sexual lubrication function. In males, it has been reported that circumcision can have positive effects, but does not necessarily prevent further flares of the disease and does not protect against the possibility of cancer. Circumcision does not prevent or cure LS; in fact, "balanitis xerotica obliterans" in men was first reported as a condition affecting a set of circumcised men, by Stühmer in 1928.

Other treatments

Carbon dioxide laser The carbon-dioxide laser (CO2 laser) was one of the earliest gas lasers to be developed. It was invented by Kumar Patel of Bell Labs in 1964 and is still one of the most useful types of laser. Carbon-dioxide lasers are the highest-power contin ...

treatment is safe and effective, and it improves symptoms over a long time, but it does not lower cancer risks.

Platelet-rich plasma Platelet-rich plasma (PRP), also known as autologous conditioned plasma, is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to remove red blood cells. Though promoted to treat an array of medical problems, evid ...

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.

Prognosis

The disease can last for a considerably long time. Occasionally, "spontaneous cure" may ensue, particularly in young girls. Lichen sclerosus is associated with a higher risk of cancer. 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 Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals. It most commonly affects the labia majora. Less often, the labia minora, clitoris, or vaginal glands are affected. Symptoms include a lump, itchiness, changes in t ...

. Lichen sclerosus is associated with 3–7% of all cases of vulvar squamous cell carcinoma. In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS. A study in men reported that "The reported incidence of penile carcinoma in patients with BXO is 2.6–5.8%".

Epidemiology

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 9–11 years old. In men, the most common age of incidence is 21–30.

History

In 1875, Weir reported what was possible vulvar or oral LS as "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 are 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 in 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, not an atrophic condition; "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 in 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. Lichen sclerosus et atrophicus was first described in 1887 by

François Henri Hallopeau __NOTOC__ François Henri Hallopeau (17 January 1842, Paris – 20 March 1919, Paris) was a French dermatologist. He studied medicine under Alfred Vulpian and Sigismond Jaccoud. He co-founded and was secretary general of the ''Société Française ...

. Since not all cases of lichen sclerosus exhibit atrophic tissue, ''et atrophicus'' was dropped in 1976 by the

International Society for the Study of Vulvovaginal Disease The International Society for the Study of Vulvovaginal Disease (ISSVD) is a non-profit organization that was founded in 1970 at the Sixth World Congress of the International Federation of Obstetricians and Gynecologists (FIGO) in New York City. I ...

(ISSVD), officially proclaiming the name ''lichen sclerosus''.

References

External links

NIAMS – Questions and Answers About Lichen Sclerosus

better medicine

Medscape Reference Author: Jeffrey Meffert, MD; Chief Editor: Dirk M Elston, MD
Medical pictures * http://www.dermlectures.com/LecturesWMV.cfm?lectureID=88 * https://web.archive.org/web/20070927210529/http://dermis.multimedica.de/dermisroot/de/34088/diagnose.htm * https://web.archive.org/web/20071008130921/http://dermnetnz.org/immune/ls-imgs.html {{DEFAULTSORT:Lichen Sclerosus Ailments of unknown cause Lichenoid eruptions