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]
Lichen sclerosus svg hariadhi.svg
Lichen sclerosus - high mag.jpg
Micrograph of lichen sclerosus showing the characteristic subepithelial sclerosus (right/bottom of image). H&E stain.
Specialty Gynaecology

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]

Contents

Signs and symptoms

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

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

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

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. [5] [14] [15]

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. [16]

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

Genetic

Lichen sclerosus may have a genetic component. A high correlation of lichen sclerosus has been reported between twins [22] [23] and between family members. [24]

Autoimmunity

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. [25] [26]

Infection

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 [27] and hepatitis C [28] are also suspected.

A link with Lyme disease is shown by the presence of Borrelia burgdorferi in LSA biopsy tissue. [29]

Hormones

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

Some findings suggest that LS can be initiated through scarring [30] or radiation, [31] [32] although those findings were sporadic and very uncommon.[ citation needed ]

Diagnosis

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

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. [34] The biopsies are also checked for signs of dysplasia. [35]

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. [36]

Treatment

Main treatment

There is no definitive cure for LS. [37] Behavior change is part of treatment. The patient should minimize or, preferably, stop scratching LS-affected skin. [38] Any scratching, stress or damage to the skin can worsen the disease. Scratching has been theorized to increase cancer risks. [39] 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. [39] [40]

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. [41] [42] [43] [44] [45] They improve or suppress all symptoms for some time, with high variance across patients, until it is required to use them again. [46] Methylprednisolone aceponate has been used as a safe and effective corticosteroid for mild and moderate cases. [47] For severe cases, it has been theorized that mometasone furoate might be safer and more effective than clobetasol. [47] 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. [48] [49] 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. [50] 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. [50]

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". [51] In a second study, of 129 patients, cancer occurred in 11% of patients, none of whom were fully compliant with corticosteroid treatment. [47] 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. [46] 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. [42] [44] [52] 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. [53] 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 [54] and does not protect against the possibility of cancer. [55] 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

Carbon dioxide laser treatment is safe and effective, and improves symptoms over the long term, [56] 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. [57]

Prognosis

The disease can last for a considerably long time. Occasionally, "spontaneous cure" may occur, [58] particularly in young girls.

Lichen sclerosus is associated with a higher risk of cancer. [59] [60] [61] [62] 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. [63] [64] Lichen sclerosus is associated with from 3 to 7% of all cases of vulvar squamous cell carcinoma. [65] In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS. [66] [67] A study in men noted that: "the reported incidence of penile carcinoma in patients with balanitis xerotica obliterans is 2.6–5.8%". [68]

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 from 9 to 11 years old. [69]

In men, the most common age of incidence is 21 to 30. [70]

History

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. [71] 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. [72]

See also

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers, among other symptoms.

Phimosis 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 teenagers and adults, it may result in pain during an erection, but is otherwise not painful. Those affected are at greater risk of inflammation of the glans, known as balanitis, and other complications.

Penile cancer, or penile carcinoma, is a cancer that develops in the skin or tissues of the penis. Symptoms may include abnormal growth, an ulcer or sore on the skin of the penis, and bleeding or foul smelling discharge.

<span class="mw-page-title-main">Lichen planus</span> Human chronic inflammatory disease

Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, but is named for its appearance. It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale, commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa. The hue may be gray-brown in people with darker skin. Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement. The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms.

<span class="mw-page-title-main">Pimecrolimus</span> Immunosuppressive drug

Pimecrolimus is an immunosuppressant drug of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema).

<span class="mw-page-title-main">Seborrheic keratosis</span> Benign skin tumor originating in keratocytes

A seborrheic keratosis is a non-cancerous (benign) skin tumour that originates from cells, namely keratinocytes, in the outer layer of the skin called the epidermis. Like liver spots, seborrheic keratoses are seen more often as people age.

<span class="mw-page-title-main">Actinic keratosis</span> Rough skin induced by UV exposure

Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure.

<span class="mw-page-title-main">Imiquimod</span> Chemical compound

Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis.

<span class="mw-page-title-main">Morphea</span> Form of scleroderma involving isolated patches of hardened skin

Morphea is a form of scleroderma that mainly involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, usually with no internal organ involvement. However, in Deep Morphea inflammation and sclerosis can be found in the deep dermis, panniculus, fascia, superficial muscle and bone.

<span class="mw-page-title-main">Vulvar cancer</span> Cancer involving the vulva

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 Bartholin's glands are affected. Symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.

<span class="mw-page-title-main">Vulvar intraepithelial neoplasia</span> Medical condition

Vulvar intraepithelial neoplasia (VIN) refers to particular changes that can occur in the skin that covers the vulva. VIN is an intraepithelial neoplasia, and can disappear without treatment. VINs are benign but if the changes become more severe, there is a chance of cancer developing after many years, and so it is referred to as a precancerous condition.

<span class="mw-page-title-main">Balanitis circinata</span> Medical condition

Balanitis circinata is a skin condition comprising a serpiginous ring-shaped dermatitis of the glans penis. While circinate balanitis is one of the most common cutaneous manifestations of reactive arthritis, it can also occur independently. Topical corticosteroid therapy is the most commonly used treatment, and topical calcineurin inhibitors have also been used successfully.

<span class="mw-page-title-main">Balanitis plasmacellularis</span> Medical condition

Balanitis plasmacellularis, also known as balanitis circumscripta plasmacellularis, Zoon balanitis, or plasma cell balanitis, is a cutaneous condition characterized by a benign inflammatory skin lesion characterized histologically by a plasma cell infiltrate.

Pseudoepitheliomatous keratotic and micaceous balanitis, (PKMB) is a cutaneous condition characterized by skin lesions on the glans penis that are wart-like with scaling. It can present as a cutaneous horn. PKMB is usually asymptomatic, with occasional irritation, burning sensation, fissuring, or maceration.

Postinflammatory hypopigmentation is a cutaneous condition characterized by decreased pigment in the skin following inflammation of the skin.

<span class="mw-page-title-main">Kraurosis vulvae</span> Medical condition

Kraurosis vulvae or vulvar lichen sclerosus (VLS) is a cutaneous condition characterized by atrophy and shrinkage of the skin of the vagina and vulva often accompanied by a chronic inflammatory reaction in the deeper tissues.

<span class="mw-page-title-main">International Society for the Study of Vulvovaginal Disease</span> Non-profit organization

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. It is composed of health care professionals from different areas, including, gynecologists, dermatologists, general practitioners, physiotherapist, nurse practitioners, etc. devoted to the study, investigation, and treatment of vulvovaginal diseases.

<span class="mw-page-title-main">Topical glucocorticoids</span>

Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory, antimitotic, and immune-system suppressing actions through various mechanisms.

Laser-assisted drug delivery (LADD) is a drug delivery technique commonly used in the dermatology field that involves lasers. As skin acts as a protective barrier to the environment, the absorption of topical products through the epidermis is limited; thus, different drug delivery modalities have been employed to improve the efficacy of these treatments. The use of lasers in LADD has been shown to enhance the penetration of drugs transdermal, leading to a higher absorption rate, limited systemic effects, and reduced duration of treatment. Although this technique has evolved in the past decade due to its efficacy through scientific research and clinical practice, there remain some limitations regarding the safety aspect that needs to be taken into consideration.

References

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  2. ↑ "Lichen sclerosus". Autoimmune Registry Inc. Retrieved 14 June 2022.
  3. 1 2 3 Meffert, Jeffrey J; Davis, Brian M; Grimwood, Ronald E (March 1995). "Lichen sclerosus". Journal of the American Academy of Dermatology. 32 (3): 393–416. doi:10.1016/0190-9622(95)90060-8. PMID   7868709.
  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. 1 2 3 4 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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  7. ↑ Laymon, CW (1951). "Lichen sclerosus et atrophicus and related disorders". A.M.A. Archives of Dermatology and Syphilology. 64 (5): 620–627. doi:10.1001/archderm.1951.01570110090013. PMID   14867888.
  8. ↑ National Vulvodynia Association. "Vulvodynia Fact Sheet". Vulvodynia Media Corner. National Vulvodynia Association. Retrieved 16 June 2012.
  9. ↑ Gutierrez-Ontalvilla, Patricia (2019). "The Female Sexual Function Index to assess patients with moderate to severe vulvar lichen sclerosus". European Journal of Dermatology. 29 (4): 430–431. doi:10.1684/ejd.2019.3580. PMID   31625922. S2CID   204775452.
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  13. ↑ Birenbaum, D.L.; Young, R.C. (2007). "High prevalence of thyroid disease in patients with lichen sclerosus". The Journal of Reproductive Medicine. 52 (1): 28–30. PMID   17286064.
  14. 1 2 Kravvas, Georgios; Muneer, Asif; Watchorn, Richard E.; Castiglione, Fabio; Haider, Aiman; Freeman, Alex; Hadway, Paul; Alnajjar, Hussain; Lynch, Magnus; Bunker, Christopher B. (2022-06-01). "Male genital lichen sclerosus, microincontinence and occlusion: mapping the disease across the prepuce". Clinical and Experimental Dermatology. 47 (6): 1124–1130. doi:10.1111/ced.15127. ISSN   1365-2230. PMID   35150005.
  15. ↑ Panou, E.; Panagou, E.; Foley, C.; Kravvas, G.; Watchorn, R.; Alnajjar, H.; Muneer, A.; Bunker, C. B. (2021-09-09). "Male genital lichen sclerosus associated with urological interventions and microincontinence: a case series of 21 patients". Clinical and Experimental Dermatology. 47 (1): 107–109. doi:10.1111/ced.14869. ISSN   0307-6938. PMID   34499360.
  16. ↑ Kravvas, Georgios; Bunker, Christopher (2024-06-04). "The acronymisation of lichen sclerosus". Skin Health and Disease. 4 (4): e401. doi:10.1002/ski2.401. ISSN   2690-442X. PMC   11297449 . PMID   39104644.
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  18. ↑ Nair, PragyaAshok (2017). "Vulvar lichen sclerosus et atrophicus". Journal of Mid-life Health. 8 (2): 55–62. doi: 10.4103/jmh.jmh_13_17 . ISSN   0976-7800. PMC   5496281 . PMID   28706405.
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  21. ↑ Gupta, Vishal; Gupta, Somesh (2017-01-12). "Genital lichen sclerosus developing around 'ectopic' urethral orifices supports the role of occlusion and urine in its pathogenesis". International Journal of STD & AIDS. 28 (9): 940–942. doi:10.1177/0956462416688159. ISSN   0956-4624. PMID   28081682.
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  24. ↑ Sherman, V.; McPherson, T.; Baldo, M.; Salim, A.; Gao, X.H.; Wojnarowska, F. (Sep 2010). "The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study". Journal of the European Academy of Dermatology and Venereology. 24 (9): 1031–1034. doi:10.1111/j.1468-3083.2010.03572.x. PMID   20202060. S2CID   1358288.
  25. ↑ Meyrick Thomas, R.H.; Ridley, C.M.; McGibbon, D.H.; Black, M.M. (1988). "Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women". British Journal of Dermatology. 118 (1): 41–46. doi:10.1111/j.1365-2133.1988.tb01748.x. PMID   3342175. S2CID   37200022.
  26. ↑ Fruchter, R.; Melnick, L.; Pomeranz, M.K. (2017-03-27). "Lichenoid vulvar disease: A review". International Journal of Women's Dermatology. 3 (1): 58–64. doi:10.1016/j.ijwd.2017.02.017. ISSN   2352-6475. PMC   5419035 . PMID   28492056.
  27. ↑ Drut, R.M.; Gomez, M.A.; Drut, R.; Lojo, M.M. (1998). "Human papillomavirus is present in some cases of childhood penile lichen sclerosus: an in situ hybridization and SP-PCR study". Pediatric Dermatology. 15 (2): 85–90. doi:10.1046/j.1525-1470.1998.1998015085.x. PMID   9572688. S2CID   10110510.
  28. ↑ Yashar, S.; Han, K.F.; Haley, J.C. (2004). "Lichen sclerosus-lichen planus overlap in a patient with hepatitis C virus infection". British Journal of Dermatology. 150 (1): 168–169. doi:10.1111/j.1365-2133.2004.05707.x. PMID   14746647. S2CID   9261207.
  29. ↑ Eisendle, K.; Grabner, T.G.; Kutzner, H. (2008). "Possible Role of Borrelia burgdorferi Sensu Lato Infection in Lichen Sclerosus". Archives of Dermatology. 144 (5): 591–598. doi:10.1001/archderm.144.5.591. PMID   18490585.
  30. ↑ Pass, C.J. (1984). "An unusual variant of lichen sclerosus et atrophicus: delayed appearance in a surgical scar". Cutis. 33 (4): 405. PMID   6723373.
  31. ↑ Milligan, A.; Graham-Brown, R.A.; Burns, D.A. (1988). "Lichen sclerosus et atrophicus following sunburn". Clinical and Experimental Dermatology. 13 (1): 36–37. PMID   3208439.
  32. ↑ Yates, V.M.; King, C.M.; Dave, V.K. (1985). "Lichen sclerosus et atrophicus following radiation therapy". Archives of Dermatology. 121 (8): 1044–1047. doi:10.1001/archderm.121.8.1044. PMID   4026344.
  33. ↑ Jędrowiak, Anna; Kobusiewicz, Aleksandra; Trznadel-Grodzka, Ewa; Kaszuba, Andrzej (2018). "Dermoscopic findings in extragenital lichen sclerosus". Our Dermatology Online. 9 (2): 197–199. doi: 10.7241/ourd.20182.24 . ISSN   2081-9390.
    - "Figures - available via license: CC BY 4.0"
  34. ↑ Lichen Sclerosus et Atrophicus at eMedicine
  35. ↑ Shelley, W. B.; Shelley, E. D.; Amurao, C. V. (2006). "Treatment of lichen sclerosus with antibiotics". International Journal of Dermatology. 45 (9): 1104–1106. doi:10.1111/j.1365-4632.2006.02978.x. PMID   16961523. S2CID   27778016.
  36. ↑ Depasquale, I.; Park, A.J.; Bracka, A. (2000). "The treatment of balanitis xerotica obliterans". BJU International. 86 (4): 459–465. doi:10.1046/j.1464-410X.2000.00772.x. ISSN   1464-4096. PMID   10971272. S2CID   32219826.
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  39. 1 2 Scurry, J. (March 1999). "Does lichen sclerosus play a central role in the pathogenesis of human papillomavirus negative vulvar squamous cell carcinoma? The itch-scratch-lichen sclerosus hypothesis". International Journal of Gynecological Cancer. 9 (2): 89–97. doi:10.1046/j.1525-1438.1999.99016.x. PMID   11240748.
  40. ↑ Todd, P.; Halpern, S.; Kirby, J.; Pembroke, A. (1994). "Lichen sclerosus and the Kobner phenomenon". Clinical and Experimental Dermatology. 19 (3): 262–263. doi: 10.1111/j.1365-2230.1994.tb01183.x . ISSN   0307-6938. PMID   8033394. S2CID   29331610.
  41. ↑ Dalziel, K.L.; Millard, P.R.; Wojnarowska, F. (1991). "The treatment of vulval lichen sclerosus with a very potent topical steroid (clobetasol Propionate 0.05%) cream". British Journal of Dermatology. 124 (5): 461–464. doi:10.1111/j.1365-2133.1991.tb00626.x. ISSN   0007-0963. PMID   2039723. S2CID   44975544.
  42. 1 2 Garzon, Maria C.; Paller, Amy S. (1999). "Ultrapotent Topical Corticosteroid Treatment of Childhood Genital Lichen Sclerosus". Archives of Dermatology. 135 (5): 525–8. doi:10.1001/archderm.135.5.525. ISSN   0003-987X. PMID   10328191.
  43. ↑ Dahlman-Ghozlan, Kristina; Hedbla, Mari-Anne; von Krogh, Geo (1999). "Penile lichen sclerosus et atrophicus treated with clobetasol dipropionate 0.05% cream: A retrospective clinical and histopathologic study". Journal of the American Academy of Dermatology. 40 (3): 451–457. doi:10.1016/S0190-9622(99)70496-2. ISSN   0190-9622. PMID   10071317.
  44. 1 2 Neill, S.M.; Lewis, F.M.; Tatnall, F.M.; Cox, N.H. (2010). "British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010". British Journal of Dermatology. 163 (4): 672–682. doi: 10.1111/j.1365-2133.2010.09997.x . ISSN   0007-0963. PMID   20854400. S2CID   16634027.
  45. ↑ Neill, S.M.; Tatnall, F.M.; Cox, N.H. (2002). "Guidelines for the management of lichen sclerosus". British Journal of Dermatology. 147 (4): 640–649. doi:10.1046/j.1365-2133.2002.05012.x. ISSN   0007-0963. PMID   12366407. S2CID   31834145.
  46. 1 2 Renaud-Vilmer, Catherine; Cavelier-Balloy, Bénédicte; Porcher, Raphaël; Dubertret, Louis (2004). "Vulvar Lichen Sclerosus". Archives of Dermatology. 140 (6): 709–712. doi:10.1001/archderm.140.6.709. ISSN   0003-987X. PMID   15210462.
  47. 1 2 3 Bradford, J.; Fischer, G. (2010). "Long-term management of vulval lichen sclerosus in adult women". Australian and New Zealand Journal of Obstetrics and Gynaecology. 50 (2): 148–152. doi:10.1111/j.1479-828X.2010.01142.x. ISSN   0004-8666. PMID   20522071. S2CID   43273940.
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  50. 1 2 Chi, Ching-Chi; Kirtschig, Gudula; Baldo, Maha; Brackenbury, Fabia; Lewis, Fiona; Wojnarowska, Fenella (2011-12-07). "Topical interventions for genital lichen sclerosus". The Cochrane Database of Systematic Reviews. 2011 (12): CD008240. doi:10.1002/14651858.CD008240.pub2. ISSN   1469-493X. PMC   7025763 . PMID   22161424.
  51. ↑ Lee, Andrew; Bradford, Jennifer; Fischer, Gayle (2015). "Long-term Management of Adult Vulvar Lichen Sclerosus". JAMA Dermatology. 151 (10): 1061–7. doi: 10.1001/jamadermatol.2015.0643 . ISSN   2168-6068. PMID   26070005.
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  56. ↑ Windahl, T. (2009). "Is carbon dioxide laser treatment of lichen sclerosus effective in the long run?". Scandinavian Journal of Urology and Nephrology. 40 (3): 208–211. doi:10.1080/00365590600589666. ISSN   0036-5599. PMID   16809261. S2CID   36979154.
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  58. ↑ Smith, S.D.; Fischer, G. (2009). "Childhood onset vulvar lichen sclerosus does not resolve at puberty: a prospective case series". Pediatric Dermatology. 26 (6): 725–9. doi:10.1111/j.1525-1470.2009.01022.x. PMID   20199450. S2CID   205677253.
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  61. ↑ Barbagli, G.; Palminteri, E.; Mirri, F.; Guazzoni, G.; Turini, D.; Lazzeri, M. (2006). "Penile carcinoma in patients with genital lichen sclerosus: a multicenter survey". Journal of Urology. 175 (4): 1359–1363. doi:10.1016/S0022-5347(05)00735-4. PMID   16515998.
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  66. ↑ Rotondo, J.C.; Borghi, A.; Selvatici, R.; Magri, E.; Bianchini, E.; Montinari, E.; Corazza, M.; Virgili, A.; Tognon, M.; Martini, F. (2016). "Hypermethylation-Induced Inactivation of the IRF6 Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus". JAMA Dermatology. 152 (8): 928–33. doi:10.1001/jamadermatol.2016.1336. PMID   27223861.
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  70. ↑ Kizer, William S.; Prarie, Troy; Morey, Allen F. (January 2003). "Balanitis Xerotica Obliterans: Epidemiologic Distribution in an Equal Access Health Care System". Southern Medical Journal. 96 (1): 9–11. doi:10.1097/00007611-200301000-00004. PMID   12602705. S2CID   45454913.
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