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 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. Several studies have recently identified the presence of autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1). This may be associated with histologic evidence of vasculitis in some cases and may lead to reduplication of the basement membrane in blood vessel walls. The exact role of these antibodies and the changes seen in the microvasculature are currently under investigation. 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 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 will improve with puberty, although other expressions of vulvodynia may persist. 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.
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 studies have linked borrelial or other infections with lichen sclerosus, yet other studies have disputed this. This concept has reemerged with European reports demonstrating Borrelia more readily in lichen sclerosus cases using "focus-floating microscopy" than conventional histology. 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. Still, other polymerase chain reaction–based studies show no increased incidence of borrelial infection.
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. Two cases have been reported to follow genital wart treatment with imiquimod.
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. Work is now underway to identify any patient subsets or particular presentations of lichen sclerosus that would warrant autoimmune screening. 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.
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....
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 potent 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.
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 potent 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.
Circumcision may benefit male lichen sclerosus and the phimosis that may accompany it. Vulvar surgery is not recommended unless an associated malignancy is present. 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. Narrow-band UVB, psoralen plus UVA (PUVA), and photodynamic therapy using a photosensitizer with laser light activation are also reported to be anecdotally beneficial by various authors.
Consultations with the following specialists may be helpful:
One study suggests patients with lichen sclerosus might have a higher rate of positive patch tests to spices and flavorings. Older literature suggests that diets that lower the acidity in the urine may benefit female genital lichen sclerosus. These latter studies were not reproducible, and no dietary recommendations 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 min and washed off. Every 2-3 wk, the time applied may be increased by about 15 min until either therapeutic effect or limiting adverse effects are noted. If a patient is applying the medication for 3 h 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.
Clinical Context: Class I superpotent topical steroid, Suppresses mitosis and increases 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. 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: An adrenocorticosteroid derivative suitable for application to 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.[22, 23]
Clinical Context: Retinoic acid analog, like etretinate and isotretinoin. Etretinate is main metabolite and has demonstrated clinical effects close to those seen with etretinate. Mechanism of action is unknown. Has been reported to benefit both symptoms and induce resolution of lesion. 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: Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A.
Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. Has been reported to benefit both symptoms and may help resolution of 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: Mechanism of action in atopic dermatitis is not known. Reduces itching and inflammation by suppressing release of cytokines from T cells. 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, may inhibit release of preformed mediators from skin mast cells and basophils and may down-regulate expression of FCeRI on Langerhans cells. Indicated in dermatitis patients as young as 2 years. Drugs of this class are more expensive than topical corticosteroids. Available as an ointment in concentrations of 0.03% and 0.1%.
Clinical Context: First nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. Derived from ascomycin, a natural substance produced by Streptomyces hygroscopicus var. ascomyceticus. Selectively inhibits 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 not observed in clinical trials, a potential advantage over topical corticosteroids. 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. Recently, 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.
Inpatient care generally is not required unless for surgery for malignancy or to relieve urinary obstruction is planned.
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.
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:
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.