Lichen Sclerosis Atrophicus – Causes, Symptoms, Treatment

Lichen Sclerosis Atrophicus (LSA) or, simply, lichen sclerosis, is a disorder characterized by an atrophic epidermis, altered collagen in the superficial dermis, and an overlying white or white-blue appearance to the skin. The terms balanitis xerotica obliterans and kraurosis vulvae have been applied to genital lesions of LSA in men and women, respectively. The pathogenesis of LSA is poorly understood, but the increased incidence of LSA with other autoimmune diseases (e.g., morphea) and the presence of autoantibodies directed against extracellular matrix protein 1 suggest LSA is an autoimmune disorder.

Kraurosis vulva 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.[rx]

Lichen Sclerosis (LS) is a chronic inflammatory disease. It was first described by Hallopeau in 1881.  In 1976, the International Society for the Study of Vulvovaginal Disease adopted the term lichen sclerosis. LS is a mucocutaneous autoimmune disorder characterized by hypopigmentation and skin atrophy. It involves most commonly the genital skin, less often the extragenital sites. LS is more common in women than in men. It may cause phimosis or scarring of the vaginal introitus. The diagnosis is based on the clinical features, but it is often confirmed by biopsy. The lesions can evolve towards the destruction of anatomic structures, functional impairment, and a potential risk for malignant evolution. Thus, treatment and long term follow-up are mandatory.

Another Name

Since then, multiple names have been used to describe this condition such as leukoplakia, kraurosis vulvae, balanitis xerotica obliterans, and lichen sclerosis atrophicus.

Causes of Lichen Sclerosis Atrophicus

  • LS is considered to be an autoimmune condition; however, its etiology remains unclear. Given its association with other autoimmune diseases such as alopecia areata, vitiligo, autoimmune thyroiditis, and pernicious anemia, its etiology is probably multifactorial. Further etiologic factors have been implicated such as genetic susceptibility, infectious agents such as spirochetes, sex hormone, and the Koebner phenomenon. Furthermore, recent data demonstrated a high prevalence of lichen sclerosis associated with morphea. 
  • The underlying pathogenesis of LS includes an infiltrate of activated T cells releasing interleukin 4 (IL 4) and transforming growth factor β (TGF β). So, these cytokines activate fibroblasts producing significantly altered collagen leading to fibrosis. Besides, the pathogenesis includes vascular damage by the decrease in the number of capillaries.
  • Interleukin 1 (IL 1) and interleukin one receptor antagonist (IL 1ra) may also be included in the pathogenesis of lichen sclerosis as well as an increased number of monoclonal T lymphocyte CD4 +, lymphocyte T dendritic CD1a + cells, macrophages, mast cells, and decreased number of T lymphocyte CD3 +.
  • Another hypothesis has been suggested such as an increased number of circulating IgG autoantibodies targeting extracellular matrix 1 (ECM 1) protein leading to widespread deposition of hyaline material in the dermis. 

Symptoms of Lichen Sclerosis Atrophicus

  • The reduction in structural complexity of vulvar tissue commonly occurs with advancing age, which is manifest externally by drying, shriveling and white patches. Formally known as kraurosis vulvae.
  • Often asymptomatic; less commonly, itching, dyspareunia, dysuria and tenderness.
  • LSA may present at any age, from pediatric to geriatric age groups.
  • The condition is more common in women.
  • The anogenital region alone is affected in about 50% of cases, the anogenital and extragenital disease is present in about 25% of cases, and only extragenital areas are affected in about 25% of cases.
  • Extragenital LSA is common on the neck, wrists, and inframammary areas.
  • Anogenital LSA in girls and women often demonstrates an hourglass-like or figure-eight configuration that surrounds the genitalia and anal region.
  • Early LSA may be pruritic or asymptomatic.
  • Primary lesions quickly evolve into white atrophic areas, with variable telangiectasias.
  • Some cases demonstrate the surrounding brown hyperpigmentation.
  • Variable features include hyperkeratosis and follicular plugging, fissures, blister formation hemorrhage, and ulceration.
  • Phimosis is a complication in uncircumcised men, and urethral stricture may also occur.
  • Squamous cell carcinoma is a rare complication with chronic genital LSA.

Diagnosis of Lichen Sclerosis Atrophicus

LS has a specific histologic pattern characterized by a band-like lymphocytic infiltrate below a zone of dermal edema and orthokeratotic hyperkeratosis. Histopathology findings vary depending on disease duration. In earlier stages, it shows vacuolar degeneration of the basal layer, hyalinization of subepithelial collagen, decreased elastic fibers in the upper dermis, and dilated blood vessels under the basement membrane. In older lesions, histology shows a reduced number of mononuclear cells and dispersed patchy islands of mononuclear cells within the hyalinized dermis.

History and Physical

LS affects most commonly the genital site and less often the extragenital area. Typical lesions begin as a sharply demarcated erythema that becomes thin, hypopigmented, ivory-white, porcelain-like, and sclerotic plaques. Plaques may become later thickened due to repeated excoriations. Itch is the main symptom and is often worse at night. Other lesions may include telangiectasias, purpura, fissures, ulcerations, and edema. Typical complaints commonly include significant pruritus, local burning sensation, pain, painful defecation. Constipation is frequent in children but rarely seen in adults. However, lesions can be asymptomatic. Genital lesions begin around the periclitoral hood. The affected area varies from a small and single area to a large area involving the entire region of the vulva, perineum, and perianus assuming a typical aspect of ‘keyhole sign.’

You Might Also Read  Mango Fruit; Types, Nutritional Value, Uses, Mango Health Benefits

However, LS usually spares the vagina and cervix. In girls, LS presents commonly with irritation and soreness although it can mimic sexual abuse. However, LS and sexual abuse can coexist. Visual lichen sclerosis exhibits the Koebner phenomenon at sites of trauma; sexual abuse can aggravate lesions of LS.  Male genital LS (boys and men) occurs in the foreskin, glans penis, and the coronal sulcus penis. Extragenital lesions occur on any part of the skin and usually asymptomatic. The most commonly involved areas are inframammary areas, neck, wrists, thighs, upper back, and shoulders. The involvement of the oral mucosa appears clinically as bluish-white papules on the buccal mucosa or under the tongue.

Evaluation

The diagnosis is based on taking a careful history including the autoimmune diseases in the patient and family, the examination of the mucosas, extragenital skin, and completed by a gynecological exam. Thus, the diagnosis of LS is usually clinical. But in some cases, a biopsy can be performed. However, atypical histology does not rule out the diagnosis.

Biopsies should be performed in case of:

  • Atypical clinical presentation
  • Suspected malignancy
  • Nonresponse, after an appropriate duration, to recommended first-line treatment

The workup of the condition should include investigation of thyroid function, and according to symptoms investigation of the other autoimmune diseases.

Treatment of Lichen Sclerosis Atrophicus

The aims of the treatment are relief of the symptoms, stopping the atrophy, prevention of scar formation, and anatomical distortion, as well as malignant transformation. The therapy includes general care, topical treatments, systemic treatments, and surgical procedures. It is fundamental to inform the patient to avoid the use of irritating products such as soap and to prefer emollients to break the itch-stretch cycle.

For genital LS, the gold standard treatment is three months application of high potency topical steroids (clobetasol propionate). Second-line therapies include topical calcineurin inhibitors and imiquimod. In men, early circumcision may be recommended. Surgery is indicated only for the treatment of complications associated with lichen sclerosus. For extragenital LS, therapeutic modalities are limited and include phototherapy, ultrapotent topical steroids, tacrolimus ointment 0, 1%, and systemic steroids or methotrexate. Follow-up examinations must be kept indefinitely. 

There is no definitive cure for LS.[] Behavior change, such as good hygiene and minimizing scratching, is an important part of treatment,[] so a more realistic goal is to control pruritus rather than resolution of the lesion. Various treatment modalities have been tried with varied results.


Topical Treatment

Hormonal therapy

  • Estrogen is an effective treatment for postmenopausal vulvovaginal atrophy and should be considered in women with dyspareunia, labial fusion, or epidermal thinning due to estrogen deficiency but not as primary therapy of LS. Moisturizers and estrogens help in dryness and atrophy
  • Topical testosterone (2%) and progesterone (2%) were mainstays of treatment for decades and were reported to induce remission of LS. It acts by reducing inflammation and helps to relieve symptoms and in some cases, resolves the lesion, but androgenic side effects such as clitoral enlargement, hirsutism, acne vulgaris, and amenorrhea are common.

Topical steroids

VLS responds to ultrapotent topical corticosteroids, i.e, clobetasol propionate or mometasone furoate, though the clinical appearance does not reverse, the patient gets symptomatic relief and it prevents scarring. Clobetasol or clobetasol propionate 0.05% ointment is a Class I superpotent topical steroid which suppresses mitosis, increases the synthesis of proteins, decreases inflammation, and causes vasoconstriction. It is given daily at night for 6–12 weeks and then one to three times per week for maintenance.

Females should be evaluated regularly to see for skin atrophy or any malignant change. Prepubertal LS in girls may resolve spontaneously although some of them may suffer from various types of vulvodynia in adulthood.

Topical calcineurin inhibitors

Tacrolimus (0.1%) and pimecrolimus (1%) have a role as maintenance therapy but not as effective as potent topical corticosteroids and may be useful as alternative treatment options. It reduces itching and inflammation by suppressing the release of cytokines from T-cells and inhibits transcription for genes that encode interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, which are involved in the early stages of T-cell activation. It also inhibits the release of preformed mediators from skin mast cells and basophils and downregulates the expression of FCeRI on Langerhans cells. Pimecrolimus is derived from ascomycin, a natural substance produced by Streptomyces hygroscopicus var. ascomycetous which selectively inhibits the production and release of inflammatory cytokines from activated T-cells by binding to cytosolic immunophilin receptor macrophilia-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release.[]

You Might Also Read  Allergic Contact Dermatitis, Causes, Symptoms, Treatment

Topical retinoids

Topical tretinoin (0.025%) and tazarotene (0.01%) have off-label indications in LS. They act by downregulation of fibroblast function. Especially in genital areas, short-contact therapy is used in which the gel is initially applied for 15 min and washed off. Every 2–3 weeks, application time is increased by 15 min until therapeutic effects are noted.

In an observational series, topical use of tretinoin improved the symptoms, gross appearance, and histopathologic features of LS with minimal side effects.[]

Vitamin D analogs

Calcitriol, calcipotriene, and calcipotriene plus betamethasone helped some patients with localized sclerotic diseases. They can be irritating over genitals which require alternate-day therapy and should be used with caution in patients having compromised renal function.[]

Topical TRPM8

There is a single case report of the use of topical Sicilian in LS with relief in pruritus. Iselin is a TRPM8 receptor antagonist similar to menthol but with a higher affinity to the TRPM8 receptor.[,]

Topical avocado and soybean extracts

Borghi et al.[] suggest topical avocado and soybean extracts as alternative treatments for mild-to-moderate LS in patients wishing to avoid corticosteroids.

Results in their study provide evidence that the topical and dietary supplements exert anti-inflammatory, antifibrotic, emollient, and lenitive actions and are effective alternatives in the treatment of mild-to-moderate VLS.

Topical oxatomide

It helps relieve pruritus through its antihistamine effects, but the course of the disease is not affected.[]

Intralesional therapy

Injection of triamcinolone acetonide 20 mg directly into the thickened hypertrophic plaques of VLS once per month for 3 months[] after topical anesthetic help to minimize patient discomfort. Intralesional injection of adalimumab has also found to be beneficial.[]

Lights and Lasers

Phototherapy

Narrow-band ultraviolet B and psoralen plus ultraviolet A

A single study of ultraviolet A1 (UVA1) in seven women with VLS that had not been controlled by topical steroids[] reported initial improvement in five patients although two relapsed and the others required ongoing treatment with topical steroids. Studies have compared ultrapotent topical corticosteroids with the calcineurin inhibitors showing more efficacy of clobetasol propionate which works better compared with UVA1 phototherapy.

Photodynamic therapy using a photosensitizer

Successful treatment of VLS with photodynamic therapy (PDT) has been reported.[] In an open study of ten patients treated with two sessions of PDT, all patients reported some improvement in symptoms of VLS (itching, burning, and pain).[]

In an open study of PDT for VLS (topical 20% 5-aminolevulinic acid, argon laser light, and one to three treatments), 10 of 12 patients derived significant improvement.[] It caused significant burning although itching improved in 8 of 12 women. Another study demonstrated good symptomatic benefit in six of ten patients treated with aminolevulinic acid-PDT using a bioadhesive patch.[]

Cryotherapy

Cryotherapy of affected genital lesions after one or a series of treatments shows improvement. In one small study of 12 patients with VLS and severe intractable itch, 75% obtained symptom relief with cryotherapy.[]

Laser

Tissue-vaporizing carbon dioxide lasers, nonablative lasers such as the pulsed dye, and erbium-doped yttrium aluminum garnet lasers have been reported to benefit LS symptomatically but did not stop the disease from recurring. There is a report showing benefit in 17 out of 31 cases of untreated LS using frequencies of 5–8 MHz with focused ultrasound.[]

Systemic Therapy

Retinoids

Retinoids appear to reduce connective tissue degeneration in LS. However, the use of these agents is limited by significant and potentially harmful side effects including cheilitis, xerosis, teratogenicity, elevated liver enzymes, hypertriglyceridemia, abdominal pain, and alopecia. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization.

Oral acitretin (20–30 mg/day for 16 weeks) was effective in one randomized trial.[] Doses of 8–30 mg daily for 4 months have been used which gave benefits both in symptoms and also induce resolution of lesions. The mechanism of action of systemic retinoids in LS particularly in genital LS is not clear; mostly, it acts by downregulation of fibroblast function.

Hydroxychloroquine

It is reported to be effective in widespread genital and extragenital LSA, with conflicting results.[]

You Might Also Read  Scabies, Causes, Symptoms, Diagnosis, Treatment

Hydroxycarbamide (hydroxyurea)

Hydroxycarbamide is an antineoplastic drug used in myeloproliferative disorders. It inhibits T-lymphocyte proliferation and gamma interferon production and has antiretroviral properties. It is used in LS in the dose of 1 g daily reducing pruritus and soreness in 6 months.[]

Cyclotron

The cyclotron is a low molecular weight interferon-inducing substance that has antiviral, immunomodulating, and anti-inflammatory effects. A prospective randomized study involved sixty patients with chronic dystrophic diseases of the vulva (45–65 years); cyclotron given intramuscular on days 1, 2, 4, 6, 8, 10, 12, 16, 20, and 23 was reported to induce rapid remission, improvement of QoL, and psychosocial function.[]

Cyclosporine

Cyclosporine has been used in only ten patients with VLS.[] Three patients had a significant improvement, five had some response, and two had no response.

Potassium Para-aminobenzoate

One report of five patients with LS at various sites and resistant to numerous other therapies documented good improvement with potassium para-aminobenzoate (4–24 g daily, in divided doses) in all five.[]

A small number of women initially have a partial response to medical treatment but have ongoing burning, irritation, and pain. In these cases, obtain cultures to exclude superinfection by Staphylococcus, Streptococcus, or Candida. The patient may have bacterial cellulitis, vulvar candidiasis, or vaginal candidiasis, which requires treatment with appropriate antibiotics or antimycotic drugs.


Diet

Twenty-three patients also received dietary supplements with Vitamin E and para-aminobenzoic acid showed improvement.[]

Surgery

VLS can be surgically excised, but mutilating gynecologic surgery is usually not recommended. The rationale behind surgical therapy is primarily to treat those patients who did not respond or responded poorly to medical treatment, secondarily to postinflammatory sequelae, and prevent the development of invasive carcinoma of the vulva.

Surgical intervention in LS is done to release a buried clitoris, to separate fused labia, or to widen a narrowed introitus in the case of pain or sexual dysfunction. V-Y advancement flap is an effective method for the reconstruction of the perineal region. This technique will allow the expansion of the vaginal orifice with good cosmetic results and rapid healing after surgery.

Introit stenosis, posterior fissuring, and scarring at the fourchette can be treated by vulvoperineoplasty.[] Since vaginal tissue is not affected by LS, part of the vaginal wall is used in the repair to prevent recurrent adhesions and fissuring at the introitus. Adhesions at the fourchette which cause dyspareunia can be extirpated. Adhesions burying the clitoris can result in the formation of painful pseudocysts. Clitoral adhesions are released with delicate knife strokes. Reformation of adhesions can be prevented by resection of a fragment of the clitoral hood in the shape of a tricorn.[]

Other points that need to be considered treating VLS are as follows:

  • Menopausal women may have symptoms related to atrophy and dryness, which will respond to topical estrogen cream and moisturizers
  • A diagnosis of superimposed vulvodynia should be considered if pain persists despite resolution of pruritus and dermal changes. It is likely that vulvodynia represents neuropathic pain, which is pain arising from abnormal neural activity secondary to disease, irritation, or injury of the nervous system that persists in the absence of ongoing disease or acute injury.
  • An allergy to the topical medication may be present. A topical steroid with a different base or consultation with an allergy specialist should be considered.

Counseling

According to the National Vulvodynia Association, women with VLS or any vulvovaginal condition experience feelings of isolation, hopelessness, depression, anxiety, anger, and low self-image. Some women are unable to continue working, any physical activity, or sexual relations.

Psychological counseling is very much needed in patients of VLS. Education relating to sexual dysfunction and dyspareunia may be required. Patients should be educated on what changes (e.g., ulceration) might indicate malignant transformation so that immediate consultation can be done.

Counseling involves self-care to be taken by patient themselves such as:

  • Avoid washing with soap or to use an emollient soap
  • Carefully dry the area after passing urine to reduce the contact of urine or using a moisturizer or soft paraffin as a barrier cream to protect skin from exposure to urine
  • If sexual intercourse is painful because of tightening at the entrance to the vagina, use of lubricants and vaginal dilators if required
  • Keep an eye on your skin. Regular self-examination is very important. If any skin change develops which does not respond to steroid creams, or there is any skin thickening, soreness, or ulceration lasting more than 2 weeks, consult without delay and get a biopsy done to rule out skin cancer.

References