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 - 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 (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 foreskin or glans can be cured by either medical or surgical treatment. [4]

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, and 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. [5]

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 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. [6] [7] 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. [8]

Several risk factors have been proposed, including autoimmune diseases, infections and genetic predisposition. [9] [10] There is evidence that LS can be associated with thyroid disease. [11]

Genetic

Lichen sclerosus may have a genetic component. A high correlation of lichen sclerosus has been reported between twins [12] [13] and between family members. [14]

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. Furthermore, there seems to be a higher prevalence of other autoimmune diseases such as diabetes mellitus type 1, vitiligo, alopecia areata, and thyroid disease. [15] [16]

Infection

Both bacterial as well as 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 [17] and hepatitis C [18] are also suspected.

A link with Lyme disease is shown by the presence of Borrelia burgdorferi in LSA biopsy tissue. [19]

Hormones

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

Local skin changes

Some findings suggest that LS can be initiated through scarring [20] or radiation, [21] [22] although these 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, as it is sometimes not recognized and misdiagnosed as thrush or other problems and not correctly diagnosed until the patient is referred to a specialist when the problem does not clear up.[ citation needed ]

A biopsy of the affected skin can be done to confirm diagnosis. When a biopsy is done, hyperkeratosis, atrophic epidermis, sclerosis of dermis and lymphocyte activity in dermis are histological findings associated with LS. [24] The biopsies are also checked for signs of dysplasia. [25]

It has been noted that clinical diagnosis of BXO 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. [26]

Treatment

Main treatment

There is no definitive cure for LS. [27] Behavior change is part of treatment. The patient should minimize or preferably stop scratching LS-affected skin. [28] Any scratching, stress or damage to the skin can worsen the disease. Scratching has been theorized to increase cancer risks. [29] 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. [29] [30]

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. [31] [32] [33] [34] [35] They improve or suppress all symptoms for some time, which highly varies across patients, until it is required to use them again. [36] Methylprednisolone aceponate has been used as a safe and effective corticosteroid for mild and moderate cases. [37] For severe cases, it has been theorized that mometasone furoate might be safer and more effective than clobetasol. [37] Recent studies have shown that topical calcineurin inhibitors such as tacrolimus can have an effect similar to corticosteroids, but its effects on cancer risks in LS are not conclusively known. [38] [39] 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. [40] 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. [40]

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". [41] In a second study, of 129 patients, cancer occurred in 11% of patients, none of which were fully compliant with corticosteroid treatment. [37] 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. [36] 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. [32] [34] [42] 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. [43] 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 flares of the disease [44] and does not protect against the possibility of cancer. [45] 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. [3]

Other treatments

Carbon dioxide laser treatment is safe and effective, and it improves symptoms over a long time, [46] 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. [47]

Prognosis

The disease can last for a considerably long time. Occasionally, "spontaneous cure" may ensue, [48] particularly in young girls.

Lichen sclerosus is associated with a higher risk of cancer. [49] [50] [51] [52] 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. [53] [54] Lichen sclerosus is associated with 3–7% of all cases of vulvar squamous cell carcinoma. [55] In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS. [56] [57] A study in men reported that "The reported incidence of penile carcinoma in patients with BXO is 2.6–5.8%". [58]

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. [59]

In men, the most common age of incidence is 21–30. [60]

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. [3]

Lichen sclerosus et atrophicus was first described in 1887 by François Henri Hallopeau. [61] 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 (ISSVD), officially proclaiming the name lichen sclerosus. [62]

See also

Related Research Articles

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References

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  23. ↑ 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"
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  26. ↑ 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.
  27. ↑ Chi, CC; Kirtschig, G; Baldo, M; Lewis, F; Wang, SH; Wojnarowska, F (Aug 2012). "Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus". Journal of the American Academy of Dermatology. 67 (2): 305–12. doi:10.1016/j.jaad.2012.02.044. PMID   22483994.
  28. ↑ "ACOG Practice Bulletin No. 93: Diagnosis and Management of Vulvar Skin Disorders". Obstetrics & Gynecology. 111 (5): 1243–53. May 2008. doi: 10.1097/AOG.0b013e31817578ba . PMID   18448767.
  29. 1 2 Scurry (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.
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  32. 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.
  33. ↑ Dahlman-Ghozlan, Kristina; Hedblad, 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.
  34. 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.
  35. ↑ 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.
  36. 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.
  37. 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.
  38. ↑ Li, Y; Xiao, Y; Wang, H; Li, H; Luo, X (Aug 2013). "Low-concentration topical tacrolimus for the treatment of anogenital lichen sclerosus in childhood: maintenance treatment to reduce recurrence". Journal of Pediatric and Adolescent Gynecology. 26 (4): 239–42. doi:10.1016/j.jpag.2012.11.010. PMID   24049806.
  39. ↑ Maassen, MS; van Doorn, HC (2012). "[Topical treatment of vulvar lichen sclerosus with calcineurin inhibitors]". Nederlands Tijdschrift voor Geneeskunde. 156 (36): A3908. PMID   22951124.
  40. 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.
  41. ↑ 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.
  42. ↑ Fistarol, Susanna K.; Itin, Peter H. (2012). "Diagnosis and Treatment of Lichen Sclerosus". American Journal of Clinical Dermatology. 14 (1): 27–47. doi:10.1007/s40257-012-0006-4. ISSN   1175-0561. PMC   3691475 . PMID   23329078.
  43. ↑ Smith, Yolanda R; Haefner, Hope K (2004). "Vulvar Lichen Sclerosus". American Journal of Clinical Dermatology. 5 (2): 105–125. doi:10.2165/00128071-200405020-00005. ISSN   1175-0561. PMID   15109275. S2CID   22448081.
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  45. ↑ Powell, J.; Robson, A.; Cranston, D.; Wojnarowska, F.; Turner, R. (2001). "High incidence of lichen sclerosus in patients with squamous cell carcinoma of the penis". British Journal of Dermatology. 145 (1): 85–89. doi:10.1046/j.1365-2133.2001.04287.x. ISSN   0007-0963. PMID   11453912. S2CID   24738069.
  46. ↑ 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.
  47. ↑ Casabona, Francesco; Gambelli, Ilaria; Casabona, Federica; Santi, Pierluigi; Santori, Gregorio; Baldelli, Ilaria (2017). "Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life". International Urology and Nephrology. 49 (4): 573–580. doi:10.1007/s11255-017-1523-0. ISSN   0301-1623. PMID   28161837. S2CID   11499796.
  48. ↑ Smith SD, 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.
  49. ↑ Nasca, MR; Innocenzi, D; Micali, G (1999). "Penile cancer among patients with genital lichen sclerosus". Journal of the American Academy of Dermatology. 41 (6): 911–914. doi:10.1016/S0190-9622(99)70245-8. PMID   10570372.
  50. ↑ Poulsen, H; Junge, J; Vyberg, M; Horn, T; Lundvall, F (2003). "Small vulvar squamous cell carcinomas and adjacent tissues. A morphologic study". APMIS. 111 (9): 835–842. doi:10.1034/j.1600-0463.2003.1110901.x. PMID   14510640. S2CID   23716949.
  51. ↑ 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.
  52. ↑ Gulin, Sandra Jerkovic; Lundin, Filippa; Seifert, Oliver (2023-09-11). "Comorbidity in patients with Lichen sclerosus: a retrospective cohort study". European Journal of Medical Research. 28 (1): 338. doi: 10.1186/s40001-023-01335-9 . ISSN   2047-783X. PMC   10494448 . PMID   37697418.
  53. ↑ Rotondo JC, Borghi A, Selvatici R, Mazzoni E, Bononi I, Corazza M, Kussini J, Montinari E, Gafà R, Tognon M, Martini F (2018). "Association of Retinoic Acid Receptor β Gene With Onset and Progression of Lichen Sclerosus-Associated Vulvar Squamous Cell Carcinoma". JAMA Dermatology. 154 (7): 819–823. doi:10.1001/jamadermatol.2018.1373. PMC   6128494 . PMID   29898214.
  54. ↑ van de Nieuwenhof, HP; van der Avoort, IA; de Hullu, JA (2008). "Review of squamous premalignant vulvar lesions". Critical Reviews in Oncology/Hematology. 68 (2): 131–156. doi:10.1016/j.critrevonc.2008.02.012. PMID   18406622.
  55. ↑ Henquet, CJ (Aug 2011). "Anogenital malignancies and pre-malignancies". Journal of the European Academy of Dermatology and Venereology. 25 (8): 885–95. doi:10.1111/j.1468-3083.2010.03969.x. PMID   21272092. S2CID   24203150.
  56. ↑ Rotondo JC, 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.
  57. ↑ Halonen, Pia; Jakobsson, Maija; Heikinheimo, Oskari; Riska, Annika; Gissler, Mika; Pukkala, Eero (2017). "Lichen sclerosus and risk of cancer". International Journal of Cancer. 140 (9): 1998–2002. doi: 10.1002/ijc.30621 . ISSN   0020-7136. PMID   28124469.
  58. ↑ Pietrzak, Peter; Hadway, Paul; Corbishley, Cathy M.; Watkin, Nicholas A. (2006). "Is the association between balanitis xerotica obliterans and penile carcinoma underestimated?". BJU International. 98 (1): 74–76. doi:10.1111/j.1464-410X.2006.06213.x. ISSN   1464-4096. PMID   16831147.
  59. ↑ Fistarol, Susanna K (2013). "Diagnosis and treatment of lichen sclerosus: an update". Journal of the American Academy of Dermatology. 14 (1): 27–47. doi:10.1007/s40257-012-0006-4. PMC   3691475 . PMID   23329078.
  60. ↑ 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.
  61. ↑ Hallopeau, H (1887). "Du lichen plan et particulièrement de sa forme atrophique: lichen plan scléreux". Annales de Dermatologie et de Syphiligraphie (8): 790–791.
  62. ↑ Friedrich Jr., EG (1976). "Lichen sclerosus". The Journal of Reproductive Medicine. 17 (3): 147–154. PMID   135083.

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