Penile lichen sclerosus (balanitis xerotica obliterans)

Authors


David Clouston, Focus Pathology, Ground Floor, 60 Wilson Street, South Yarra, Victoria 3141, Australia. e-mail: David.Clouston@focuspathology.com.au

Abstract

What's known on the subject? and What does the study add?

The clinical presentation and complications of lichen sclerosus are well known. What is less well known is the true incidence of the condition. The published figures are all based on attendance at general medical clinics or specialist clinics, but it is likely that the true incidence is much higher than this reported incidence as many men will not present to the doctor for treatment. The other uncertainty is the relationship of lichen sclerosus to the subsequent development of cancer of the penis. As pointed out in the paper, it is likely that between 4% and 8% of men with this condition will develop squamous cell cancer of the penis. However, it is unclear if lichen sclerosus itself causes the development of squamous cell cancer or if it is due to coexistent infection with human papillomavirus.

This review provides a concise summary of the clinical and pathological features of the disease and describes its current medical and surgical treatment. It brings together a number of papers which have addressed the association of lichen sclerosus with squamous cell carcinoma of the penis and shows that the likely incidence of carcinoma is approximately 4–8% in men with this condition.

SUMMARY

Penile lichen sclerosus, also known as balanitis xerotica obliterans, is a chronic inflammatory condition of the penis which can occur at all ages. The inflammation leads to the formation of white plaques most commonly on the foreskin or penis, and can lead to inability to retract the foreskin or blockage to the flow of urine. Cancer may occur rarely.

Penile lichen sclerosus is a progressive, sclerosing, inflammatory dermatosis of the glans penis and foreskin which is of uncertain aetiology. Recent studies have shown a link between lichen sclerosus and squamous cell carcinoma of the penis. In this review, we discuss the clinical presentation, pathology and current approach to treatment of this condition.

Abbreviations
HPV

human papillomavirus

SCC

squamous cell carcinoma.

INTRODUCTION

Penile lichen sclerosus is a progressive, sclerosing, inflammatory dermatosis of the glans penis and foreskin (prepuce) of uncertain aetiology that results in significant morbidity. Lichen sclerosus was originally described by Stuhmer in 1928 as balanitis xerotica obliterans (BXO), a term of Greek derivation, with xeros meaning dry and obliterare, to efface. However, penile or male genital lichen sclerosus is the preferred terminology, as lichen sclerosus occurs in both males and females, and in anogenital and extragenital sites. In a review of the literature, Meffert et al. [1] found lichen sclerosus was reported in 4280 women compared with 691 men, with 4308 cases involving the genitals, 805 in extragenital sites and 355 cases involving both genital and extragenital sites. In men, lichen sclerosus occurs most commonly on the glans penis and prepuce and less commonly on the scrotum. Perianal involvement is extremely rare in male patients with lichen sclerosus. In up to 20% of patients, there may be extragenital lesions, particularly on the upper trunk, shoulders and upper arms. Extragenital lesions are not seen in penile lichen sclerosus occurring in boys [2].

In this review, we will discuss the pathogenesis and clinical presentation of penile lichen sclerosus and the current approach to treatment.

INCIDENCE

The true incidence of penile lichen sclerosus is unknown but is likely to be more common than the quoted figures. Kizer et al. [3] found an incidence of 0.07% in an unselected cohort of 153 432 patients presenting to an outpatient clinic in Brookes Army Medical Centre in the USA. Penile lichen sclerosus occurs across all ages from as early as 6 months of age.

Penile lichen sclerosus accounts for a significant proportion of patients with penile disease. In a study of 357 men presenting to a specialist penile dermatosis clinic, penile lichen sclerosus was present in 52 men (15%), of whom 51 were uncircumcised [4]. Similarly, Yardley et al. [5] found penile lichen sclerosus in 34% of circumcision specimens from boys between the ages of 3 months and 16 years.

AETIOLOGY AND PATHOGENESIS

The aetiology of male genital lichen sclerosus is unknown, but it is most probably multifactorial. Like most penile inflammatory dermatoses, penile lichen sclerosus occurs most frequently in uncircumcised or late circumcised middle-aged men. The role of the foreskin is unknown, but it most likely contributes to the development of disease through the accumulation of epithelial debris and secretions in the fold between the foreskin and penis proximal to the coronal sulcus. This accumulated material then causes chronic physical irritation, chronic balanitis or subclinical trauma with subsequent Koebner phenomenon, where skin lesions appear along the lines of trauma [1,6]. Alternatively, the accumulated material may harbour an infectious agent which is yet to be identified. Borrelia Burgdorferi, a spirochaete, was implicated by studies in Austria [7], but this organism has not been identified in subsequent studies in America, Britain or Australia.

Penile lichen sclerosus is an inflammatory dermatosis with subsequent fibrosis causing the late complications of the disease. The inflammatory infiltrate is predominantly a T cell infiltrate infiltrating the basal epidermis and superficial dermis. Initially, the T cells are CD4+ T helper cells, but in the active stage of the disease when basal vacuolar change occurs the T cells are predominantly CD8+, CD57+ cytotoxic T cells, which is a profile generally associated with viruses, autoimmune diseases or malignancy [8]. However, the eliciting antigen has not been identified.

In a small number of cases, penile lichen sclerosus has been associated with autoimmune diseases including diabetes mellitus, vitiligo and alopecia areata, and patients have had various autoantibodies, including antinuclear, thyroid antimicrosomal, antigastric parietal cell, anti-adrenal cortex, anti-smooth muscle and antimitochondrial antibodies [4,9,10]. However, Meffert et al. [1] make the comment that the association with these autoimmune diseases is so infrequent that testing for autoimmune diseases is not indicated in patients with penile lichen sclerosus. A study of human leukocyte antigen (HLA) associations showed a predominance of HLA DQ7 with DR11 and DR12 present less commonly [9].

The presence of human papillomaviruses (HPV) has been reported in some cases of childhood penile lichen sclerosus, with HPV identified by PCR in 52% of cases in one study of 23 cases and 64% of 11 cases [2,11]. The HPV serotypes include HPV 6, 16 and 18, as well as HPV 8, 23, 36, 38 and DL285. Whether the lichen sclerosus is directly attributable to HPV infection or whether lichen sclerosus merely promotes HPV infection is unclear. Adults with penile lichen sclerosus have not been demonstrated to have a higher incidence of HPV infection.

Hormonal influences may contribute to the development of vulvar lichen sclerosus but have not been demonstrated in penile lichen sclerosus to date. Childhood vulvar lichen sclerosus frequently resolves with the onset of menarche when there is an increase in testosterone production in genital skin.

There may be a genetic basis in some cases of lichen sclerosus, including penile lichen sclerosus. However, no well defined genetic association has been identified in the majority of cases of penile lichen sclerosus.

HISTOPATHOLOGY

The early stage in the development of penile lichen sclerosus is a moderately heavy lymphocytic infiltrate in the basal epidermis and superficial dermis, associated with basal vacuolar change in the epidermis (Fig. 1). In cases with pronounced vacuolar change, the epidermis may detach from the dermis with the formation of haemorrhagic bullae. As the lesion develops, the epidermis becomes atrophic with surface hyperkeratosis. During the development of the lesions, there is loss of elastic fibres in the papillary dermis and the dermal inflammatory infiltrate is displaced downwards by subepidermal oedema, which is subsequently replaced by fibrosis.

Figure 1.

An early lesion of penile lichen sclerosus showing an infiltrate of lymphocytes in the basal epidermis with vacuolar change and damage in the basal keratinocytes. There is early hyperkeratosis across the surface. Normal epidermis can be seen on the right of the photomicrograph. (Haematoxylin and eosin; original magnification 400×.)

Therefore, the classic lesion associated with penile lichen sclerosus occurs relatively late and is characterized by epidermal atrophy with surface hyperkeratosis, a thickened basement membrane and an underlying broad zone of subepidermal oedema with homogenization of collagen, which becomes more sclerotic over time. At this time, the inflammatory infiltrate is relatively light and located deep to the dermal fibrosis (Fig. 2).

Figure 2.

A late lesion of penile lichen sclerosus showing epidermal atrophy with a thick band of hyperkeratosis across the surface. There is a broad band of homogenized collagen expanding the dermis and there is very little residual inflammation, which is seen under the collagen band. (Haematoxylin and eosin; original magnification 100×.)

CLINICAL PRESENTATION

Penile lichen sclerosus may be asymptomatic. The commonest symptoms associated with penile lichen sclerosus are whitening or reddening of the glans penis, foreskin (prepuce) and coronal sulcus with thickening (induration) of the glans and foreskin. These symptoms are not specific, with the differential diagnosis given in Table 1. Thickening of the foreskin may lead to either difficulty or total inability to retract the foreskin (phimosis) in uncircumcised males. In other patients retraction of the foreskin results in constriction of the distal penile shaft, referred to as ‘wasting’[12]. Phimosis can cause difficulty with erection and sexual intercourse and occasionally difficulty with voiding. Rarer complaints include purpura and telangiectases of the glans, pruritus, paraesthesia (a burning sensation), dysuria, urinary retention and renal failure. Rarely lichen sclerosus leads to severe atrophy of the glans penis, making differentiation from morphoea (localized scleroderma) difficult.

Table 1.  Differential diagnosis for penile lichen sclerosus
▪ Balanitis (bacterial or fungal)
▪ Carcinoma in situ
▪ Squamous cell carcinoma (early)
▪ Plasma cell balanitis (Zoon's balanitis)
▪ Lichen planus
▪ Leukoplakia
▪ Psoriasis
▪ Balanitis circinata (of Reiter's syndrome)
▪ Contact dermatitis
▪ Cicatricial pemphigoid
▪ Fixed drug reaction
▪ Scleroderma

The initial physical manifestations are subtle, with non-specific erythematous or hypopigmented macules or papules. These discrete pale or erythematous macules and papules coalesce into atrophic ivory, white or purple-white plaques with well defined margins. Superficial dilated blood vessels (telangiectases) and small purpura may be visible. Lichen sclerosus most commonly affects the glans penis and prepuce, such that a sclerotic white ring at the tip of the prepuce is diagnostic. The frenulum, urethral meatus, fossa navicularis (most distal dilated portion of the urethra) and penile shaft may become involved.

With further disease progression, the glans penis may become adherent to the prepuce with fibrous replacement of the coronal sulcus and frenulum, leading to phimosis. Urethral stenosis may occur in patients with urethral lesions, with urinary retention as a rare complication. Urinary retention may be severe enough to cause retrograde damage to the posterior urethra and to the bladder and kidneys.

Usually the disorder is slowly progressive and may have periods of quiescence.

COMPLICATIONS

The complications of penile lichen sclerosus arise from progressive sclerosis and include phimosis, painful erection, reduced urinary flow and urinary retention. Rarely vesicles and bullae may develop.

It is still debated whether penile lichen sclerosus is a premalignant disease. Vulval lichen sclerosus is considered by many experts as a premalignant disease. Vulval squamous cell carcinoma (SCC) has been associated with vulval lichen sclerosus, even if the risk is less than 5% of all cases of vulval lichen sclerosus [13]. The association between SCC of the penis and lichen sclerosus has come under increasing scrutiny recently. A retrospective study from Italy reported invasive SCC or premalignant change of the penis in five of 86 men (5.8%) with a history of penile lichen sclerosus with an average duration of 17 years [14]. The same researchers re-interviewed their cohort of patients later and found a total of eight of their patients developed penile cancer, representing 9.3% of their study [15]. They concluded that ‘the association between PLS [penile lichen sclerosus] and cancer may very well be underestimated’. A retrospective study from Oxford found histological or clinical evidence of lichen sclerosus in 11 of 20 patients with SCC of the penis [16]. The authors concluded that ‘there appears to be a definite association between SCC of the penis and lichen sclerosus’. A large retrospective study from Paraguay examined the penectomy and circumcision specimens from 207 patients with carcinoma and giant condylomas and found 68 patients with evidence of lichen sclerosus (33%) but felt this probably underestimated the true association [17]. A prospective study of 155 penile carcinomas in London found evidence of lichen sclerosus in 28% of their patients [18]. A study examining the role of HPV infection in the pathogenesis of penile cancer reported lichen sclerosus in 13 of 26 patients with penile SCCs [19]. A review of circumcision specimens from 100 consecutive symptomatic male patients found invasive SCC in 11 cases [20]. In all 11 of these cases, there was evidence of lichen sclerosus, suggesting a strong association between these two diseases. Invasive SCC has occurred even 20 years after circumcision for lichen sclerosus [21], a personal observation also made by one of the authors (APH). Based on these studies, it has been estimated that the risk of malignant transformation of penile lichen sclerosis is 4–8%, similar to vulval lichen sclerosus [22]. Long-term prospective studies are needed to determine the real risk of malignant transformation of penile lichen sclerosus.

DIAGNOSIS

Lichen sclerosus is usually diagnosed clinically. A skin biopsy should be considered to exclude other similar genital diseases (such as lichen planus) and to exclude associated subclinical in situ or invasive SCC [23]. Skin biopsy increases the accuracy of diagnosis, re-enforces a long-term management plan and will prove important for participation in prospective clinical trials to provide more accurate prognostic information. A genital skin punch biopsy is a relatively simple procedure, little different from skin biopsy at other sites. While male patients are often apprehensive about skin biopsy of the genitalia, reassurance that the procedure is relatively painless after infiltration of a local anaesthetic and suturing the biopsy site allays anxiety and minimizes any complications.

TREATMENT

MEDICAL

Topical corticosteroid preparations are the main stay of treatment for penile lichen sclerosus. Rapid improvement is common if the most potent topical steroid available is used. There is no single correct regime for the use of topical steroids. Betamethasone diproprionate 0.05% in ‘optimized vehicle’ base or clobetasol proprionate 0.05% cream or ointment are suitable potent topical corticosteroids. The potent topical steroid should be applied once daily to the glans and foreskin. (It may be appropriate to recommend twice daily application to the affected area of the glans if circumcised as any topical steroid is rapidly rubbed off by clothing). After 6–8 weeks, reduce the application of the topical steroid to every second day and review the patient at 12–16 weeks to assess response to treatment. Often a less potent topical steroid (such as mometasone aceponate 0.1% cream) can be substituted if there is a good response. The less potent topical steroid can often be reduced further to application only once or twice weekly. A poor response is often due to poor compliance or fear of use of topical steroids [13]. Encouragement to persist regularly with the use of a topical steroid treatment and reassurance of the long-term safety of topical steroids usually helps to achieve a beneficial outcome. If there is no improvement by 6 months, then use of the potent topical steroid should be abandoned. A trial of a potent topical corticosteroid should always be undertaken in uncomplicated penile lichen sclerosus before surgery. As lichen sclerosus may relapse after circumcision or meatotomy (for urethral meatal stenosis) it is worthwhile reintroducing use of the potent topical steroid soon after the surgical wounds have healed.

The topical calcineurin inhibitors pimecrolimus and tacrolimus have been used with success but should not be used as first-line therapy. Long-term safety of calcineurin inhibitors has not been established for genital disease [13]. Systemic oral corticosteroids have no role in management of penile lichen sclerosus and should be avoided. Penile dysaesthesia may respond to a low dose tricyclic antidepressant or gabapentin.

SURGICAL

Surgical treatment of penile lichen sclerosus often involves circumcision for confirmation of pathology and to ameliorate symptoms and offer cure in many cases. To date, this has been the traditional urological teaching. As already discussed, a trial of steroids may alleviate the need for surgery in selected cases, although if phimosis is an issue then a circumcision is generally required. Clearly where carcinoma in situ or invasive cancer is suspected, individual biopsies and/or circumcision must be performed. Suspicious lesions on the glans which are raised, firm and erythematous should be biopsied, as a circumcision specimen will not suffice. It should be noted that lichen sclerosus of the glans will often be assisted by circumcision, possibly due to elimination of the moisture-rich environment that can harbour precipitants. In a large case series of 287 patients with lichen sclerosus limited to the foreskin or glans treated by circumcision, 92% had cessation of symptoms and no further advancement of the disease following surgery [24].

Severe lichen sclerosus may require extensive surgery (Fig. 3) involving either glans resurfacing with grafting or complete degloving with or without split skin grafting depending on any previous circumcision [25,26]. What must always be kept in mind is that disease control, function (voiding and intercourse) and cosmesis all need to be carefully balanced. Glans resurfacing has become popular due to the high graft take rates and also because reasonable cosmesis can be obtained. In the most severe cases, penile lichen sclerosus which has been left untreated has been reported to affect the penile skin, scrotum and entire urethra [24,27].

Figure 3.

A case of severe penile lichen sclerosus involving the glans, meatus and penile shaft that has failed to respond to circumcision and steroids. A buried penis now exists (A) and the extent of glans and meatal involvement is also evident (B).

Urethral involvement is variable and may involve the meatus, navicular fossa and even the penile urethra. Thus cysto-urethroscopy may be advised in cases of potential urethral involvement to exclude other pathology and also to identify the extent of any urethral involvement with lichen sclerosus. Meatal involvement may eventually be extremely debilitating as this will result in pain, voiding difficulties and potentially effects on the bladder and upper tracts. So the obvious secondary effects of lichen sclerosus are stricturing that may require urethrotomy, dilatation or regular intermittent self-catheterization. In some instances meatoplasty, extensive urethroplasty and reconstructions are necessary. Again, topical steroids may have a role as already alluded to earlier but surgical intervention is often required [23,24,28].

Follow-up of patients with lichen sclerosus is important as the disease may recur. Interestingly lichen sclerosus may recur in the scar line of any previous surgery due to the Koebner phenomenon, where recurrent lichen sclerosus appears despite ‘clear margins’ on the original excision [6]. The vigilant examination for possible SCC and time to follow-up are uncertain. Just as with regular testicular self-examination, patients should be informed to return if any lesions recur.

OTHER TREATMENTS

The literature has mentioned other treatments for lichen sclerosus including intralesional corticosteroids, topical and intramuscular testosterone, intravenous procaine, topical oestrogen and retinoid creams, oral vitamin E, and radiation therapy [28,29,30]. Most of these are not ongoing investigations and have no studies with large numbers to support their use.

Although appealing, the use of a CO2 laser results in healing by secondary intention in most instances due to the depth of penetration of the laser [31–33]. Thus cosmesis may not be improved over surgery, particularly with glans resurfacing now available (see the Surgical section) and few reports have been published in the past decade [34].

CONCLUSION

Penile lichen sclerosus may affect the whole genital region (penile skin, prepuce, glands, scrotum) and even the anogenital region as well as the urethra. Thus it is a urological condition we need to understand. A partnership with an interested dermatologist is invaluable to identify those patients requiring surgical treatment as well as providing medical options for patients. Extensive or complex surgery may be required beyond the frequently performed circumcision, often requiring specialized techniques which should be limited to centres with experience.

It is estimated that the risk of malignant transformation of penile lichen sclerosis is 4–8%, but long-term prospective studies are needed to determine the real risk of malignant transformation of penile lichen sclerosus. With this in mind, vigilance is required in advising follow-up and timely review in patients in whom failure to respond, progression or recurrence occurs.

CONFLICT OF INTEREST

None declared.

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