Lichen sclerosus (LS) is a chronic inflammatory dermatosis that results in white plaques with epidermal atrophy and scarring. Lichen sclerosus has both genital and extragenital presentations and also goes by the names lichen sclerosus et atrophicus (dermatological literature), balanitis xerotica obliterans (glans penis presentation), and kraurosis vulvae (older description of vulvar presentation). An increased risk of squamous cell carcinoma may exist in genital disease, but the precise increase in risk and what cofactors (human papillomavirus infection or prior radiotherapy) may be involved are not yet completely defined. In patients who have been treated for vulvar cancer, the presence or absence of lichen sclerosus does not appear to affect the timing of recurrence. In large series, genital presentations, both vulvar and penile, outnumber extragenital reports by more than 5:1.
Inflammation and altered fibroblast function in the papillary dermis leads to fibrosis of the upper dermis. Genital skin and mucosa are affected most frequently, but extragenital lichen sclerosus does occur, and even rare oral presentations are reported. The role that hypoxia and ischemia have in the initial cellular and vascular damage is supported by the finding of increased glut-1 and decreased vascular endothelial growth factor (VEGF) expression in affected skin. The effect of cell-mediated cytotoxicity has been better defined at the biochemical level. Systemic disease or involvement of other organ systems, unlike scleroderma, is not described, although many more authors are describing lichen sclerosus and scleroderma as closely related entities; many cases of coexistent lichen sclerosus/scleroderma having been reported.
The population rate is unknown. Male genital lichen sclerosus is seen almost exclusively in uncircumcised or incompletely circumcised men and boys. The rate of circumcision in a given population would thus influence the rate in this subset.
Lichen sclerosus, both genital and extragenital, has no known racial predilection. A genetic predisposition, based on family clustering, is apparent.
The male-to-female ratio is 1:6, with female genital cases making up the bulk of reports.
Up to 15% of cases are in children with the majority being vulvar presentations. A study of foreskins submitted after therapeutic circumcision for phimosis revealed many cases of unrecognized lichen sclerosus. Extragenital lichen sclerosus is rare in children.
Extragenital lichen sclerosus may be asymptomatic or it may itch, although itching is not usual. Vulvar lichen sclerosus usually presents with progressive pruritus, dyspareunia, dysuria, or genital bleeding. Penile lichen sclerosus usually is preceded by pruritus but may present with sudden phimosis of previously retractable foreskin, and urinary obstruction can result.
Pertinent physical findings are limited to the skin.
Lichen sclerosus usually begins as white, polygonal papules that coalesce into plaques. Evenly spaced dells or comedolike plugs correspond to obliterated appendiceal ostia. These may be easily identified with dermoscopy, keeping in mind that other conditions such as chronic cutaneous lupus may also show follicular plugs. With time, the plugs and dells will disappear and leave a smooth, porcelain-white plaque. Skin color is white, often with a shiny porcelain appearance. Telangiectases and follicular plugs may be seen. The size of the plaque or plaques may vary widely from a few millimeters resembling lichen nitidus to the entire upper trunk.
Vulvar lichen sclerosus may progress to gradual obliteration of the labia minora and stenosis of the introitus. The most common variation occurs when the inflammation is intense enough to cause separation of a large area of epidermis, creating blisters or large, occasionally hemorrhagic, bullae. Because this occurs more often in genital cases, it may be confused with the trauma of sexual abuse or other genital ulcerative disease.
Given the high frequency of genital mucosal disease, it is surprising that more oral cases have not been reported. Those rare cases reported are usually seen in patients with widespread, generalized lichen sclerosus. Some believe that many cases of clinically diagnosed lichen planus may actually be lichen sclerosus and that isolated oral mucosal lichen sclerosus may not be as rare as is thought.
Extragenital lesions may occur anywhere on the body, although the back and shoulders are reported most commonly. Note the image below:
Extragenital lichen sclerosus demonstrating coalescing pitted white papules. Courtesy of Wilford Hall Medical Center slide files.
Female genital lesions may be confined to the labia majora but usually involve and eventually obliterate the labia minora and stenose the introitus. Often, an hourglass, butterfly, or figure-8 pattern involves the perivaginal and perianal areas, with minimal involvement of the perineum in between. Note the images below:
Lichen sclerosus demonstrating classic hourglass or figure 8 vulvar and perianal distribution. Courtesy of Wilford Hall Medical Center slide files.
More advanced vulvar lichen sclerosus; eroded areas need to be carefully examined and a biopsy sample should be taken to exclude coexistent squamous c....
Male genital lesions usually are confined to the glans penis and the prepuce or foreskin remnants. Penile shaft involvement is much less common, and scrotal involvement is rare. The initial manifestation may be a sclerotic ring at the prepuce edge. Note the image below:
Male genital lichen sclerosus may present with a sclerotic ring at the edge of the prepuce or anywhere on the glans itself. Advanced disease at the ur....
The isomorphic (Koebner) phenomenon is described in this condition, with the resultant lesions in old surgical scars, burn scars, sunburned areas, and areas subject to repeated trauma. Distribution of lichen sclerosus along the lines of Blaschko was described in an extragenital case.
The etiology and pathogenesis of lichen sclerosus is unknown but may include genetic, infectious, environmental, and hormonal factors.
Several older studies have linked borrelial or other infections with lichen sclerosus, yet most other studies have disputed this, with polymerase chain reaction–based studies showing no increased incidence of borrelial infection.
Genetic and autoimmune factors have been explored without identification of consistent, reproducible patterns, although autoantibodies to ECM1 have now been reported by several independent authors. Increased circulating autoantibodies may be as high as 28%, comparable to the rate seen in bullous lichen planus. Baldo et al reported that more than 40% of vulvar lichen sclerosus and lichen planus patients have reactive T cells to the NC16A domain of bullous pemphigoid antigen 180 ; however, other studies suggest that the level of autoantibodies is poorly correlated to disease activity and response to treatment. Women with lichen sclerosus have a higher rate of associated autoimmune disease (odds ratio, 4.3), especially for autoimmune thyroid disease, compared with men.
Local irritation or trauma seems to play a role in some cases of lichen sclerosus, especially in genetically predisposed individuals. However, the sequence of events that leads to the altered fibroblast function, microvascular changes, and hyaluronic acid accumulation in the upper dermis continues to be researched.
Oral contraceptives in premenopausal women have been shown to give a relative risk of 2.5, which suggests an altered hormonal axis as a possible contributory factor.
Lichen sclerosus may occur in association with other inflammatory conditions including psoriasis. This is surprising because the histopathological findings of lichen sclerosus and psoriasis are so dissimilar.
Diagnosis may often be made on clinical appearance, and ancillary examinations such as dermoscopy may help confirm the diagnosis. Biopsy should be performed in questionable cases, and, in follow up, biopsy samples from nonhealing ulcerations or masses should be examined exclude malignant transformation.
Skin biopsy (punch preferred) is the primary study to perform for diagnosis of lichen sclerosus. Despite the presence of autoantibodies described in several studies, an autoimmune workup (eg, antinuclear antibody, vitamin B-12 levels, thyroid function tests) is still not generally recommended because the frequency of multiple autoimmune diseases associated with lichen sclerosus is not high enough to justify the expense of screening all patients. For the same reason, Borrelia antibody titers are not recommended, as they would not clearly influence therapy and, in most studies, are not strongly associated with lichen sclerosus, especially in the United States.
Imaging studies are not needed unless urinary obstruction secondary to severe, stenosing genital lichen sclerosus is present. Intravenous pyelogram might be appropriate in this situation.
Punch biopsy in the most mature area of the lesion usually is diagnostic. In genital biopsies, snip excisions may suffice. Suturing the wound, especially when using braided suture, which is less likely to poke sensitive skin, leads to more rapid healing than allowing self-granulation.
Ulcerative or vegetative genital lesions may need to be biopsied more than once to screen for squamous cell carcinoma. Epidermal hyperplasia and/or dysplasia associated with lichen sclerosus on vulvar biopsy specimens is associated with an increased risk of malignant transformation. Overexpression of wild-type p53 is also associated with increased cancer risk as is a human papillomavirus–associated increase in p16INK4A. Contrary to this study, Paolino, et al (2013) suggest that human papillomavirus is not identified in most cases of lichen sclerosus–associated malignancy and, when it is, may be a nononcogenic type.
Classic lichen sclerosus demonstrates a lichenoid infiltrate in the dermal-epidermal junction, compact hyperkeratosis with stratum corneum, which often is thicker than the greatly effaced epidermis. Remarkable edema in the papillary (upper) dermis is replaced by a dense, homogenous fibrosis as the lesion matures. Extensive and deeper biopsies may show areas more consistent with scleroderma than classic lichen sclerosus. Note the images below.
Typical lichen sclerosus histology demonstrating homogenized edematous papillary (upper) dermis and effaced epidermis.
Late lichen sclerosus may show less edema in the upper dermis and more sclerosis throughout the dermis. Involvement of the lower dermis or fat may occ....
Both dermoscopy and confocal microscopy are in vivo methods of recognizing typical histologic findings for different skin conditions. Lacarruba et al (2015) discuss typical findings in lichen sclerosus, including the appearance of epidermal atrophy and follicular plugging.
Asymptomatic extragenital lichen sclerosus usually requires no treatment as control of pruritus rather than resolution of the lesion, which is a more realistic goal of therapy.
Genital lichen sclerosus may respond to ultrapotent (superpotent) topical corticosteroids although the patient should be warned that the clinical appearance does not always reverse, even if symptoms are relieved. It is widely reported that prepubertal lichen sclerosus in girls may resolve spontaneously although some of these patients may go on to suffer from various types of vulvodynia in adulthood. Treatment will necessarily be prolonged, and short-term treatments often lead to suboptimal control of findings and symptoms.
Periodically, a report will suggest that areas of vulvar lichen sclerosus be surgically excised or ablated with a laser as a prophylactic measure. Most authors dispute this concept and do not recommend mutilating gynecologic surgery for what, in most patients, is a benign disorder. It is true, however, that circumcision may resolve male genital lichen sclerosus, although the use of ultrapotent topical steroids may obviate the need for surgery in such cases.
The calcineurin inhibitors (ie, tacrolimus, pimecrolimus) have been found to help some patients, especially with genital lichen sclerosus, but they do not work as fast or as effectively as potent topical corticosteroids. They may have a role in maintenance therapy, although several case reports have described that they were not effective.
Narrow-band UVB, psoralen plus UVA (PUVA), and photodynamic therapy[17, 18] using a photosensitizer with laser light activation are also reported to be anecdotally beneficial.
A variety of studies have compared ultrapotent topical corticosteroids with the calcineurin inhibitors and high-, medium-, and low-potency corticosteroids, with the usual result that while other agents may have benefits, the best results are seen with the strongest topical medications and with relatively few adverse effects.[19, 20] Clobetasol propionate also worked better when compared with UVA-1 phototherapy.
Borghi et al (2014) suggest topical avocado and soybean extracts as alternative treatments for mild-to-moderate lichen sclerosus in patients wishing to avoid corticosteroids. The patients also received dietary supplements containing the same substances along with vitamin E and para-aminobenzoic acid. In a small study of 23 patients, most reported improvement.
Other anecdotal therapies include intralesional injection of adalimumab and topical tretinoin.
Circumcision may benefit male lichen sclerosus and the phimosis that may accompany it. Vulvar surgery has not been recommended unless an associated malignancy is present. More recent articles have suggested that surgical release of clitoral phimosis and labial adhesions may improve some patients with severe dyspareunia, although the numbers were small and some surgical complications were noted.[24, 25] Extragenital lesions may be excised, but some caution should be taken as lichen sclerosus has arisen in old surgical scars.
A variety of destructive procedures have been reported to be of benefit, although follow-up studies often do not show the same efficacy as original pilot reports. Not just tissue-vaporizing carbon dioxide lasers, but also nonablative lasers such as the pulsed dye and Er:YAG lasers, have been reported to benefit persons with lichen sclerosus. Cryotherapy of affected genital lesions is also reported to reduce the area involved after one or a series of treatments.
Consultations with the following specialists may be helpful:
There are no reproducible studies relating to diet or reactions to any particular foods, spices, or flavorings. For that reason, no dietary recommendations or restrictions currently are proposed.
Lichen sclerosus–associated dyspareunia or painful erections may limit sexual activity. No specific activity limits or exercises are recommended. An author in the 1930s suggested that tight underwear and bicycle seats were the cause of lichen sclerosus in girls, but neither of these has been validated as the cause of lichen sclerosus in later studies.
Topical testosterone was mainstay of treatment for female genital lichen sclerosus for decades, although it was never shown useful in male genital or extragenital cases. More recent studies suggest it may not be any more efficacious than placebo. Systemic therapies, including anti-Borrelia antibiotics, potassium benzoate, penicillamine, and systemic steroids, have not proven reliably effective.
Systemic retinoids have been useful in limited studies with isotretinoin, etretinate, and acitretin. Topical corticosteroids, especially in the superpotent class, have been found to be useful in genital lichen sclerosus in both sexes and in all age groups. These have been used long term (weeks to months) or daily, without significant adverse cutaneous effects, although patients should always be monitored regularly for adverse effects (especially atrophy of nearby uninvolved areas).
Therapy with tazarotene (Tazorac) is off label for this medication in this location and for this indication. Especially in genital and other occluded areas, short-contact therapy is used, in which the gel (or cream) is initially applied for 15 minutes and washed off. Every 2-3 weeks, the time applied may be increased by about 15 minutes until either therapeutic effect or limiting adverse effects are noted. If a patient is applying the medication for 3 hours or more, they may consider leaving the medication in place. For extragenital lichen sclerosus, this may be applied and left in place. This may be done in conjunction with topical steroid use. Tazarotene has not been well studied for lichen sclerosus in children, but application should be similar to adult usage. A pregnancy test is recommended before starting therapy, and the drug is category X (contraindicated). Tazarotene may be irritating and is not likely to be tolerated on open and denuded areas.
Systemic administration of the vitamin D analogs calcitriol (Calcijex, Rocaltrol, Vectical), calcipotriene (Dovonex, Sorilux, Calcitrene), and calcipotriene plus betamethasone (Taclonex) has been shown anecdotally to be effective for generalized morphea. While not universally effective, topical forms of this category have helped some patients with localized sclerotic diseases. They can be irritating in genital and occluded areas and may require alternate-day therapy. They are usually not used as monotherapy for sclerotic disorders but, rather, are usually combined with topical corticosteroids. Daily to twice-daily application is suggested. Use with caution in patients with compromised renal function, and prolonged use of large amounts warrants laboratory monitoring (with particular attention to serum calcium values). Pediatric dosing is the same as adult dosing. These agents are pregnancy category C.
One report describes successful treatment of refractory generalized extragenital lichen sclerosus with pulsed high-dose corticosteroids combined with methotrexate. Methotrexate and other immune suppressing medications have been used, alone and in combination with topical and systemic corticosteroids. Standard dosages are used with the usual contraindications, and monitoring is recommended. Because of the risk of squamous cell carcinoma, some medications known to increase squamous cell carcinoma risk (eg, cyclosporine) should be used with caution with very careful monitoring of the patient for suspicious lesions, which should undergo biopsy immediately. The use of potent immunosuppressant medications in patients with active intraepithelial dysplasia or even significant condyloma acuminata should only be performed after careful informed consent and consideration of other options. Most of the immunosuppressant agents are pregnancy category C and D, but some are X.
Hydroxychloroquine is also reported to help some patients with widespread genital and extragenital lichen sclerosus, but even here there are some conflicting studies.
Clinical Context: Clobetasol is a class I superpotent topical steroid. It suppresses mitosis and increases the synthesis of proteins that decrease inflammation and cause vasoconstriction. Other superpotent steroids would be expected to have the same results; however, most published studies showing benefit of such medications have used clobetasol.
Pulse dosing (2 consecutive days/wk) may be used long-term, even in genital cases. On off-days, a milder steroid or emollient alone may be used. There is no additional benefit in using potent and super-potent steroids more often than daily. Especially in genital applications, twice-daily application of such a medication will more quickly lead to steroid adverse effects.
Clinical Context: Hydrocortisone topical is an adrenocorticosteroid derivative suitable for application to the skin or external mucous membranes. It has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity.
Reducing inflammation helps reduce symptoms and, in some cases, helps resolve the lesion.
Clinical Context: Acitretin is a retinoic acid analog, like etretinate and isotretinoin. Etretinate is the main metabolite and has demonstrated clinical effects close to those seen with etretinate. The mechanism of action is unknown. Acitretin has been reported to benefit both symptoms and induce resolution of lesions. Although not well studied, combining a medication in this class with a topical corticosteroid as described above may be useful in refractory cases.
Clinical Context: Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A.
Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization. Isotretinoin has been reported to benefit both symptoms and may help resolution of the lesion itself. Although not well studied, combining a medication in this class with a topical corticosteroid as described above may be useful in refractory cases.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Mechanism of action for successful effects systemic retinoids have had in lichen sclerosus (usually studied in female genital cases) is not clear but may have to do with down-regulation of fibroblast function.
Clinical Context: The mechanism of action for tacrolimus ointment in atopic dermatitis is not known. It reduces itching and inflammation by suppressing the release of cytokines from T cells. It also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, it may inhibit the release of preformed mediators from skin mast cells and basophils and may down-regulate expression of FCeRI on Langerhans cells. Tacrolimus ointment is indicated in dermatitis patients as young as 2 years. Drugs of this class are more expensive than topical corticosteroids. It is available as an ointment in concentrations of 0.03% and 0.1%.
Clinical Context: Pimecrolimus is the first nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by Streptomyces hygroscopicus var. ascomyceticus. It selectively inhibits the production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy is not observed in clinical trials, a potential advantage over topical corticosteroids. Pimecrolimus is indicated only after other treatment options have failed
Many have concerns about the use of potent topical corticosteroids in occluded areas such as the genitals. They often do not work as well or as fast as the corticosteroids when used as monotherapy, but this class of medications may have a role either as maintenance medications after steroid-driven improvement or in conjunction with them in a pulse-steroid regimen (ie, superpotent corticosteroid on weekend days and a TIM during the week). Some believe this may delay or obviate the onset of tachyphylaxis and reduce the risk of steroid atrophy. This is an off-label use for both medications. Some have raised concerns about the use of these medications long term, especially in young children and infants. The exact risks of long-term use, if any, remain to be defined, but the prescriber should be aware of the issues.
If potent topical steroids are to be used, regular follow-up is required to monitor for the occurrence of steroid atrophy. Monitor female lichen sclerosus patients for any sign of secondary or associated genital malignancy. Extragenital cases require no specific follow-up.
Inpatient care generally is not required unless for surgery for malignancy or to relieve urinary obstruction is planned.
A patient requiring surgical intervention (circumcision or cancer surgery) may require transfer to another specialist if the dermatologist or primary care physician is not competent in the procedure required.
Following are male genital, female genital, and extragenital complications:
The following issues also may arise:
Prognosis is good for more acute genital cases, especially for those in pediatric age group that may resolve spontaneously. Prognosis for improvement is poor for extragenital cases and for chronic atrophic genital disease.
Lichen sclerosus has no associated increased mortality unless the patient develops a malignancy in the area. Cancer arising in extragenital presentations is described only rarely and may be coincident with other factors. Many pediatric cases improve with puberty. In contrast, some authors suggest the rate of spontaneous resolution may be lower than 25%. Extragenital cases and many genital cases are asymptomatic except for the cosmetic aspect or pruritus. Recalcitrant cases, especially those associated with erosion or progressive scarring, may result in severe sexual dysfunction.
Education relating to sexual dysfunction and dyspareunia may be required. Patients with genital lichen sclerosus should be educated on what changes (eg, ulceration) might indicate malignant transformation and mandate an immediate reevaluation.