B burgdorferi causing lichen sclerosus?

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Lichen sclerosis: early diagnosis is the key to treatment.

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Vulvar lichen sclerosus (VLS) is a serious chronic dermatologic and

gynecologic condition associated with epithelial thinning, inflammation, and

distinctive dermal changes. The most prevalent symptom is the intense

pruritus of the vulvar area. This disease is most common in postmenopausal

women but is recently being diagnosed more frequently in premenopausal women.

Once thought to be a rare condition, VLS is now one of the most common

conditions seen in vulvar clinics. The prevalence of VLS remains unknown. The

disease is frequently misdiagnosed as chronic vaginitis. The misdiagnosis of

chronic vaginitis is easily attributed to the similarity of symptoms. During

the early stages of the disease, misdiagnosis is common because there are no

apparent skin changes [1,2]

If vulvar lichen sclerosus is left untreated there is a loss of normal vulvar

structure. As the disease progresses there is a loss of distinction between

the labia majora and minora, along with the loss of the clitoral hood.

Eventually the clitoris will be covered by the fusing labia. The perineal

area shrinks, which may preclude intercourse or result in painful

intercourse. When there is splitting of the involved skin between the vagina

and rectum this may cause painful defecation with bleeding. Excoriation of

the area occurs due to the intense pruritus [2].

While lichen sclerosus is found in both males and females and in all

age-groups [1,2], this article focuses on lichen sclerosus in females in the

vulvar area. The few articles published on this condition focus primarily on

the disease at the cellular level or on other aspects of VLS not addressed in

this article [3-8].

Epidemiology

Lichen sclerosus (LS) is found in all age groups, both male and female. The

onset of the disease may occur between 6 months of age and late adulthood.

Lichen sclerosus may appear anywhere on the body. Extrogenital sites include

the neck, shoulders, and back, and are generally asymptomatic. The most

common site in females is the vulvar and surrounding areas. Most patients are

described as Caucasian, but lichen sclerosus has been found in African,

Asian, and other dark-skinned patients. Women are diagnosed more frequently

with LS than men [2,7,8].

In uncircumcised males, LS has been reported on the prepuce. Most consider

trauma or chronic infection as the cause. Circumcision is the treatment of

choice. Ridley suggests that early circumcision may protect males against LS.

Incidences of malignancy have been reported in males [8,9].

In children, LS is more common than is currently recognized; LS affects

children from age 6 months to late adolescence. Often there is a delay in

treatment due to the inexperience of the clinician and the misdiagnosis of

sexual abuse. This is not to say that sexual abuse and VLS do not coexist but

that the trauma to the area mimics the abuse and makes diagnosis difficult

[8-10].

One problem in reporting the incidence of VLS in children or adult females is

the interchangeable terms of " genital " versus " vulva " and " perineal " versus

" groin. " Some congruity is needed in the description of involved areas [8].

Clinical Manifestations

Most female patients with VLS seek health care with complaints of severe

vulvar pruritus and are in their perimenopausal or postmenopausal years.

Other symptoms include burning pain, dyspareunia, dysuria, vaginal discharge,

and anal or genital bleeding along with labial stenosis or fusion. This is

where the misdiagnosis of vaginitis is often made [2,8].

With vaginitis (candidiasis or yeast infection), the patient complains of

severe itching, burning, and irritation in the vulvar region. A complaint of

discharge and discomfort during intercourse is also made. The labia majora is

swollen and excoriated. With bacterial vaginitis, the complaint is of a

foul-smelling discharge, irritation, and severe itching. With the symptoms

being similar in vaginitis and VLS, it is easily understood why some

misdiagnoses can occur [11].

If the patient continues to complain about pruritus, and vaginitis has been

ruled out, the clinician may want to consider VLS. The distinct tissue

changes are often the first visual indication of VLS, but only a biopsy can

confirm the diagnosis and rule out a malignancy [2].

Vulvar lichen sclerosus is not considered to be a premalignant condition,

although areas of hyperplastic epithelium changes from lichen sclerosus can

be sites of premalignant or malignant changes [2,12]. However, an increased

risk does exist. The reported incidence of squamous cell carcinoma (SCC)

ranges between 6% and 25% in women with VLS. In a more recent study of 78

cases of the carcinoma, LS was found in 61% of the women. In these women,

squamous cell carcinomas were confined to the labia minora and clitoris

[9,13].

In a review of LS cases of 4,280 females and 691 males, genital LS was the

highest at 4,308. Squamous cell carcinoma was 283 with 291 having an

autoimmune disease and another 316 having the auto-antibodies. The neck,

shoulders, and upper trunk were the most common nongenital sites reported in

805 cases [8]. The incidence of approximately 6% with genital cancer is a

relatively high incidence given the rarity of vulvar carcinoma.

In a 1995 study, it was found that of the 211 female subjects that had

histologically demonstrated VLS, three developed SCC. This study showed that

the chance of developing SCC in women with VLS is more than 300-fold higher

than that of women without VLS in the same age group [14].

The intense pruritus causes the patient to scratch, which results in

excoriation of the skin. This intense itch-scratch-itch cycle can seriously

affect one's quality of life. Scratching causes erosions to occur which cause

burning on urination. This symptom can confuse the clinician causing repeated

unnecessary urine testing all with negative results. According to some

researchers, because of this repeated trauma the areas of VLS may become

hyperplastic. These areas of hyperplastic epithelium are believed to be at

risk for SCC [2,12,13].

Pathogenesis

The exact pathogenesis of VLS is not clear, but there are many old theories

concerning the cause of lichen sclerosus. In 1903, the cause was first

described as a local interference with the blood supply to the vulvar area.

Little was written about LS until a 1952 report suggesting that women who

were " hysterical, " " excitable, " or " highly nervous " were at a greater risk of

developing VLS [8].

Two main theories exist concerning the cause of VLS. One current theory is

that VLS is caused by an infectious disease or a virus. Borrelia burgdorferi,

the causative agent in Lyme disease, was speculated to be the cause of VLS.

Even though some studies showed evidence of a Borrelia infection, the results

were conflicting and inconclusive. It was also once believed that VLS was

another manifestation of syphilis. Some patients with VLS have been diagnosed

with syphilis, but a new spirochete has become a suspect in VLS. Researchers

have found these spirochetes in the papillary dermis of 48% of patients with

VLS, especially in early cases [8,12].

The second theory involves the interaction of hormones, fibroblasts, and

changes in collagen. This theory has been studied for decades without any

universal agreement on the pathogenesis of VLS. Hormonal studies focus on the

actions of testosterone. Patients with VLS were found to have a decreased

serum level of free testosterone, androstenedione, and dihydrotestosterone. A

defect in the function of 5 [Alpha]-reductase, an enzyme that shows increased

activity in genital skin when compared to nongenital skin, is believed to be

the underlying defect predisposing these patients to VLS [7-9].

Other theories conclude that LS could be caused by the isomorphic or

" Koebner " phenomenon. This theory includes the premise that friction caused

by tight clothing may cause and spread LS. Some theorize that the trauma of

skin rubbing against skin is the trigger for genital and extragenital LS.

Early dermatologic literature states that LS occurring on the back and

shoulders is caused from brassiere straps. Also included in this theory is

that trauma, repeated masturbation, " garden variety " local flora,

mycobacteria or pneumococcus, the warm and moist area, or a low-grade

infection all play a role in the development of VLS [8].

There are also other theories relating to various mechanisms that could

affect VLS. These theories include immunologic, genetic, androgen receptor

inactivity or deficiency, and peridermal growth factor deficiency [2,7,8];

Genetic studies remain inconclusive. VLS has been reported in families, but

no consistent autosomal or X-linked genetic pattern has been found [8].

Since 1910, attempts have been made to link LS to autoimmune disorders. The

most common diseases linked to LS are thyroid disease (Graves' disease) and

type I and type II diabetes. A thyroid test is recommended in patients with

LS. In both sexes, vitiligo and alopecia areata have been reported with

genital and extragenital LS. Other immune-related conditions that are

associated with LS include: achlorhydria with and without pernicious anemia,

lichen planus, atopic dermatitis, eczema, psoriasis, polymyalgia rheumatica,

fascitis, primary biliary cirrhosis, myositis, lupus panniculitis, and

systemic lupus erythematosus [8].

One study suggested that nonsmokers were more likely to have VLS than

smokers. The androgen-elevating effect of cigarette smoking is thought to be

the cause of lower incidence of VLS in smokers [8].

Diagnosis

The vulvar area should be carefully observed in all patients with a complaint

of severe pruritus of the vaginal area (and particularly when a vaginal

infection has been ruled out). A patient with VLS will have thin, white skin,

localized to the labia minora/majora (Figures 1 and 2). The vulvar area will

also have white papules with an erythematous halo and keratotic plugging [8].

[Figure 1 and 2 ILLUSTRATION OMITTED]

Initially, VLS begins as white polygonal papules that form into plaques with

fine crinkling. These hypopigmented areas are generally seen peripherally in

the perineum, perianally, or on the external aspect of the labia majora.

There may also be a pattern of a waxy appearance of the labia minora with

speckling. As VLS progresses the fragility of the skin becomes evident by

tears in the skin along with the appearance of purpura. The area is easily

excoriated due to the constant rubbing and scratching [8,9,13].

It cannot be stressed enough that clinicians must perform a meticulous search

for VLS and other lesions especially in women with a chief complaint of

vulvar pruritus or labial dysuria during a pelvic exam. If diagnosed early,

proper treatment can be started along with appropriate follow-up care

[2,8,9,12,13].

The accuracy of a biopsy in diagnosing VLS is debatable. If the symptoms are

minimal and the skin changes are questionable, then a biopsy should be

performed to confirm VLS. Only a biopsy can rule out SCC. However, there is a

drawback to the biopsy. Sometimes in patients with subtle clinical signs, the

results of the biopsy may be difficult to interpret and a definite diagnosis

of VLS may be impossible [9,13]. If the disease is suspected, a biopsy may

confirm the diagnosis and determine if it is malignant [2].

There are other differential diagnoses that the clinician should consider

with a complaint of vulvar pruritus. Some dermatologic conditions that should

be considered are eczema, lichen simplex, and psoriasis. Neoplasia conditions

include SCC, vulvar intrepithelial neoplasia, and other malignancies. Also

with infection, the clinician should consider vaginal warts as a possible

diagnosis [3].

Treatment

Treatment begins with an effort to control the pruritus. This can be

accomplished by prescribing a medium potency steroid ointment such as

betamethasone valerate 0.1% (Beta-Val, Betatrex, Valisone, Canadian: Beben,

Betaderm, Betnesol, Celestone, Diprolent, and Diprosone). Creams are not as

effective in controlling the pruritus as ointments. The patient must apply

the ointment to the affected area 2 to 3 times daily for 2 weeks. The

clinician needs to understand that prolonged use of medium- or high-potency

steroids may cause thinning of vulvar skin outside the field of lichen

sclerosus. Superpotent steroids such as halobetasol (Ultravate) and

clobetasol (Temovate) may be used for short periods, after biopsies have

ruled out neoplastic changes. If the area becomes unresponsive to the topical

ointments, it may be necessary to inject intralesional steroids such as

triamcinolone acetonide (aristocort, azmacort, kenalog-10, Canadian:

aristocort, azmacort, kenalog, and triaderm) directly into the area [2].

Some concerns are associated with the use of super-potent topical steroids.

The steroids can relieve some symptoms in VLS especially pruritus. There have

been concerns that use of the steroids could lead to local infections but no

evidence suggests this. The steroids may cause skin thinning which is also a

symptom of VLS. Contact sensitivity to the steroids has been well documented

and must be considered prior to patient use [15].

The most common form of treatment is 2% testosterone proprionate in

petrolatum. This ointment is applied 2 to 3 times per day for up to 6 months.

After the initial treatment the testosterone is decreased to only once per

day; this is based on the patient's response to treatment and any side

effects. The patient needs to know that this is a lifelong treatment. The

side effects from the testosterone can cause clitoromegaly, hirsutism, and

the development of male characteristics [2,16].

Topical testosterone provides the best results improving gross and

histopathologic changes in the tissue. In one study conducted on 30 subjects

with VLS using testosterone, after 1 year of therapy 20 patients (66.6%) in

the testosterone group had considerable improvement, six patients (20%) were

unchanged, and four (13.4%) became worse. The pruritus was the most improved

symptom [4].

The use of topical progesterone has also been effective in the treatment of

VLS. The dose is 200 mg of progesterone in oil mixed with two ounces of

hydrophilic ointment. The success rate was only 50%. The use of topical

cyclosporine has shown some promise in patients with VLS. The dose is 200

mg/day of cyclosporine with the usual dosage of 50 mg four times/day for 8

weeks. Only three patients were evaluated in this study [12].

Some patients may benefit from sedation at night during the early phase of

the disease to help with the pruritus. Low doses of tricyclic antidepressants

help patients who are anxious or tearful. This will help the patient to rest

at night [13].

In patients that have SCC, it will be necessary to remove the affected areas.

This involves major surgery and affects the patient's body image. At one time

a vulvectomy was the primary treatment for VLS; however there was a high

incidence of recurrence of VLS after the excision. In some cases skin

grafting was attempted but VLS recurred in the grafted skin. Unless there is

a malignancy a vulvectomy is contraindicated [8,9,12].

The patient needs to have regular visits to her clinician every 3 months to

check the progression of VLS. This is very important in the early detection

of cancer. Patients with hyperplastic lesions should be seen more frequently.

Conclusion

Vulvar lichen sclerosus is frequently misdiagnosed by many clinicians. The

clinician needs to devote more care when performing a pelvic exam so that VLS

can be detected in the early stages when treatment is most helpful. This

article summarizes the diagnosis and treatment of VLS to help clinicians

understand and meet the needs of the patient with VLS in order to detect this

disease during its early stages.

REFERENCES

[1.] Dalziel KL: Effect of liche