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Balanitis Xerotica Obliterans (Male Penile Lichen Sclerosus)

Author: Kevin Carocci Author: Stephen W. Leslie Author: Elizabeth C. Hughes Editor: Gregory V. McIntosh Updated: 10/29/2024 10:47:38 PM

Introduction

Balanitis xerotica obliterans (BXO) is a form of lichen sclerosus that involves the foreskin and glans penis in affected male individuals. The condition presents as white or hypopigmented macules or atrophic papules on the penis. Involvement of the foreskin leads to atrophic skin changes with depigmentation and constriction, which can result in phimosis. In the glans, these changes result in the characteristic whitish patches and meatal stenosis.

BXO was first described as a unique entity in 1928 by Stühmer and is responsible for about 85% of all cases of acquired phimosis.[1] Urethral stricture disease and meatal stenosis are common sequelae of BXO.[2][3] For information on lichen sclerosus in women, see the companion StatPearls reference review, "Lichen Sclerosus."

Etiology

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Etiology

The etiology of BXO is mainly unknown. Possible contributing etiological factors include chronic penile inflammatory conditions, genetic predisposition, infections (such as syphilis), the Koebner phenomenon, morphea, penile trauma, diabetes, and sex hormone disorders.[4] Smoking, obesity, and cardiovascular disease have also been linked to this condition.[5]

While BXO is closely associated with several autoimmune disorders, including alopecia areata, autoimmune thyroiditis, localized scleroderma (morphea), pernicious anemia, and vitiligo, BXO is likely multifactorial.[6][7] Proposed etiologies of this disorder include various infections, penile trauma, and chronic inflammatory states. HLA-DR11, HLA-DR12, and HLA-DQ7 antigens are found more often in patients with BXO or lichen sclerosus than in controls.[8][9][10]

First described by Heinrich Koebner in 1876, the Koebner phenomenon refers to an isomorphic response in unaffected skin following cutaneous trauma, commonly observed in psoriasis.[11] The Koebner phenomenon's exact cause is unclear, but it appears to involve adhesion molecules, autoimmune antigens, cytokines, and stress proteins.[12] This condition is neither new nor unique but rather an activation of a preexisting cutaneous disorder.[13] For more information on the Koebner phenomenon, see the companion StatPearls reference, "Koebner Phenomenon." 

Most inflammatory skin disorders of the male genitalia occur in uncircumcised men or boys who undergo late (postpubertal) circumcision. The foreskin may promote chronic inflammation due to the sequestration or pooling of urine under the prepuce, which may activate the Koebner phenomenon and ultimately result in BXO.[14] Postvoid dribbling and microincontinence may contribute to the development of BXO.[15] Further evidence of this theory is demonstrated by the tendency of BXO to affect only the skin exposed to sequestered urine, as with a phimotic foreskin, while sparing other areas, such as the anogenital region.

Another theory suggests that the underlying etiology may be a hormonal disorder involving 5α-reductase, as adults with BXO generally have lower levels of androstenedione, dihydrotestosterone, and free testosterone than controls. Human papillomavirus (HPV) does not appear to be a causative factor of BXO. However, of those cases that progress to squamous cell carcinoma (SCC), 22% demonstrate evidence of HPV infection, with HPV-16 being the most prevalent genotype.[16]

Epidemiology

Reporting on the prevalence of this condition is challenging, as patients initially present to a wide range of physician specialties. Studies have reported prevalence rates of male genital lichen sclerosus to be approximately 0.1% to 0.3% (1 case per 300 to 1,000 men) overall.

In children, the consensus is that the peak age of BXO is 7 to 8 years, although the incidence in boys is thought to be significantly underestimated.[17][18][19][20] Some published reports suggest the actual incidence is 5% to 6% and as high as 8.9% in uncircumcised boys.[21][22] In adults, BXO is most often found in middle-aged and older men.[23] A large U.S. Department of Defense database found that the incidence of male lichen sclerosus more than doubled in adults older than 60.[24]

An uncircumcised status is the strongest risk factor for developing BXO, regardless of age. In one study, 98% of patients diagnosed with BXO were uncircumcised.[25] While no specific racial or ethnic predilection exists, Black and Hispanic cohorts report a higher frequency of BXO, likely due to lower circumcision rates in these populations.

Pathophysiology

Clinically, BXO is a chronic, progressive mucocutaneous autoimmune disorder characterized by hypopigmentation and skin atrophy with constriction, often resulting in phimosis or meatal stenosis.[26] At the cellular level, this dermatological disorder involves activated T cells releasing interleukin-4 (IL-4) and transforming growth factor-β, leading to abnormal collagen production with fibrosis and decreased vascularity.

Additional cytokines and cellular factors include IL-1 and IL-1 receptor antagonists; increased monoclonal CD4+ T lymphocytes, CD1a+ dendritic cells, macrophages, and mast cells; and decreased CD3+ T lymphocytes.[27] CD8+ and CD57+ lymphocytes may also be increased, along with Ki67+ and p53+ cells, resulting in keratinocytic hyperplasia.[28] Another theory has suggested that BXO may involve widespread hyaline material deposition due to immunoglobulin G autoantibodies to extracellular matrix 1 (ECM1) protein.[29]

Though usually relatively benign, BXO is now considered a non–HPV-related premalignant lesion and may undergo malignant SCC transformation if untreated.[30][31][32][33][34][35][36][37] In a retrospective review, 13.6% of patients with BXO demonstrated penile intraepithelial neoplasia (PeIN). Progression to SCC of the penis has been reported in up to 9.3% of patients with penile lichen sclerosus. This malignant progression takes an average of 17 years.[38] Conversely, a significant percentage of patients with penile SCC (28-55%) also had histological evidence of BXO.[39][40][41]

Histopathology

Early BXO is characterized by a specific histologic pattern showing a band-like lymphocytic infiltrate below a zone of dermal edema. Histology of early lesions shows a moderate lymphocytic infiltrate in the superficial dermis and basal layers of the epidermis. These features are associated with vacuolar changes in the basal epidermal layer. With progression, the papillary dermis loses elastic fibers as the epidermis becomes atrophic with superficial hyperkeratosis. Subepidermal edema, later replaced by fibrosis, pushes bands of inflammatory infiltrate deeper.[42]  

BXO lesions demonstrate abundant infiltrating cytotoxic T lymphocytes with abnormal extracellular matrix metabolism, orthokeratotic hyperkeratosis, and epidermal atrophy. Serum levels of autoimmune antibodies to extracellular matrix proteins may be present.[43] The superficial dermis often has abundant homogenized collagen with a lymphoplasmacytic infiltrate. 

Genetically, an immune-mediated TH1-specific interferon-γ–induced phenotype predisposes patients to BXO. MicroRNAs and tissue remodeling genes are overexpressed, and oxidative stress leads to DNA peroxidation, which promotes autoimmune reactions and carcinogenesis.[44]

History and Physical

BXO may initially present asymptomatically. When symptomatic, the most common presentation is hypopigmentation followed, in order, by phimosis, dysuria, voiding dysfunction, narrowed urinary stream, erythema, balanitis, circumferential scarring of the foreskin, meatal stenosis, buried penis, pain, and penile adhesions.[45] White hypopigmented lesions seen on the glans, penis, or foreskin are the most common finding. These lesions may be associated with phimosis and meatal stenosis. Complications may develop if the condition is left untreated, including dysuria, narrowed or weakened stream, urinary retention, paraphimosis, and renal failure.

Erythematous changes may also develop, appearing as well-defined lesions around the coronal sulcus, foreskin, and meatus. These lesions can progressively invade the distal urethra and fossa navicularis, resulting in urethral strictures, which may extend to the proximal urethra.[46]

A large study from the United Kingdom demonstrated that surgical referrals for a nonretractile phimotic foreskin are made appropriately. However, other forms of BXO often go unrecognized, and first-line therapy is rarely initiated in the primary care setting. Voiding dysfunction from BXO is relatively uncommon but tends to cause significant morbidity when present.

Evaluation

In a retrospective review of 380 adult patients at the Mayo Clinic, the average delay in diagnosis was over 2 years. In a separate study, the mean diagnostic delay period for patients younger than 18 was 22 months.[47]

BXO is almost always seen in uncircumcised male patients. The condition presents with white or erythematous areas on the glans, penis, or foreskin. A whitish, sclerotic lesion right around the distal lumen of the foreskin is characteristic of BXO. A similar white, sclerotic area around the urethral meatus is also highly suggestive. A biopsy may be needed in questionable cases to provide an accurate diagnosis.

Urethral stricture involvement should be suspected in patients with voiding dysfunction (weak stream) who do not have meatal stenosis and in individuals with symptoms unrelieved by meatotomy surgery. Evaluation of these patients may necessitate cystoscopy and retrograde urethrography, while uroflowmetry may be used for screening and follow-up tracking.

The diagnosis of BXO does not require specific laboratory tests. However, a serum test for syphilis may be helpful in selected cases.

Treatment / Management

Both conservative (medical) and surgical options are available for BXO treatment. As a general guide, topical steroids are used in BXO with meatal stenosis, while circumcision is more likely to be recommended for adult patients with symptomatic phimosis or a history of paraphimosis.[48] Asymptomatic patients do not require therapy.

Conservative Treatment

Topical steroids are the main treatment for symptomatic lichen sclerosus, starting initially with very high-potency compounds (see below).[49] Topical therapy is relatively ineffective in the most severe cases of BXO, which require a primarily surgical approach. Systemic oral steroids have no therapeutic benefit in BXO cases.[50](B2)

Topical steroid therapy for BXO usually proceeds as follows:

  • Very high-potency topical steroids, such as clobetasol propionate 0.05%, fluocinonide 0.1%, and halobetasol propionate 0.05%, are the initial nonsurgical treatments of choice. While practical, these medications should not be used continuously for more than 3 weeks. After that period, the frequency of application should be adjusted to once or twice a week. This regimen has been successful in over 90% of pediatric patients with phimosis or mild BXO.[51]
  • Medium-potency steroids, including amcinonide 0.1%, betamethasone dipropionate 0.05%, desoximetasone 0.05% to 0.25%, diflorasone diacetate 0.05%, fluticasone 0.005% to 0.05%, and triamcinolone acetonide 0.1% to 0.5%, may be used continuously for up to 3 months.
  • Low-potency topical steroids, such as alclometasone dipropionate 0.05%, desonide 0.05%, fluocinolone acetonide 0.01%, hydrocortisone 1% to 2.5%, and triamcinolone 0.025%, as well as commercially available over-the-counter steroid creams, do not have any specified limit for routine or continuous use.
  • Children should generally use topical steroids for less than the maximum duration allowed for adults.[52]

Betamethasone and triamcinolone are common options and typically require twice-a-day dosing. However, higher-potency topical steroids are generally recommended for initial therapy.

The patient is monitored for a response. If a good response is observed after 2 months, the frequency of topical steroids may be reduced to every other day or every 3rd day.[53] Weekly topical steroid applications may be considered after the lesion has resolved.[54][55] Topical steroid therapy combined with foreskin stretching has been used successfully in prepubertal boys with nonretractable phimosis.[56][57](A1)

Poor responses typically result from poor compliance with the application protocol, inadequate use of highly potent topical steroids, and severe cases of BXO with established scarring. Surgery, with or without a biopsy, should be considered in individuals resistant to topical therapy after 3 months.[58]

Circumcision is usually recommended in cases of severe phimosis affecting voiding or sexual performance to avoid the need for long-duration topical therapy. Histological examination of the foreskin is highly recommended in such patients.[59]

Topical calcineurin inhibitors like pimecrolimus and tacrolimus, the oral retinoid acitretin, platelet-rich plasma, and subcutaneous intralesional injections with the tumor necrosis factor inhibitor adalimumab are considered 2nd-line treatments.[60][61][62] Intraurethral steroid suppositories have demonstrated efficacy in treating urethral strictures associated with BXO.[63](A1)

Surgical Therapy

As sensitive, intimate anatomical areas are involved, patients may develop feelings of being mutilated, disfigured, or humiliated, requiring great sensitivity and respect from clinicians when discussing surgical options. Some surgical interventions for BXO, such as urethral stricture treatment, may result in long recovery periods with some degree of decreased sexual function or enjoyment, disruption of daily living activities, embarrassment, pain, and swelling.[64] In addition to the usual requirement to review surgical risks, benefits, and reasonable alternatives, patient and family preferences must be carefully considered. Indications for surgery include significant symptoms inadequately relieved by conservative measures, failure of topical therapy, suspected penile cancer, diagnostic uncertainty, or patient preference over prolonged topical treatment.(B3)

Preliminary treatment with topical steroids may be considered to reduce inflammation before surgical intervention. Persistent voiding issues, such as a weakened stream after a successful meatotomy, suggest a urethral stricture. 

A penile malignancy is suggested by unexplained ulcerations, nodules, growth of a neoplastic lump, blistering, erythema, blisters, lymphadenopathy, and failure to respond to standard therapy. Common signs and symptoms of penile malignancy include nodule or tumor growth, ulceration, blistering, hematuria, erythema, pain, purulent discharge, bleeding, lymphadenopathy, and failure to respond to treatment for presumptive inflammatory or infectious balanitis.

Circumcision

This procedure is often recommended when phimosis is significant so that it affects voiding, reduces sexual performance, or causes paraphimosis. Circumcision is almost always curative.[65] Uncircumcised children should undergo complete or radical circumcision when lichen sclerosus is suspected based on immunohistological findings of premalignant markers, such as p53 and Ki67, in affected foreskins. This precaution aims to prevent the later development of SCC in adulthood. Half of all BXO cases treated with partial or incomplete circumcision have been linked to disease recurrence.[66] For more information, see the companion StatPearls reference review on "Circumcision."

Preputioplasty of the foreskin, together with intralesional triamcinolone, has been suggested as an acceptable alternative to circumcision in boys with BXO.[67] Initial reports indicate high levels of patient satisfaction with this procedure as an alternative to traditional circumcision.[68] No data supports the use of this procedure in adults with BXO, and long-term outcomes are unavailable for this therapy. The lack of research on preputioplasty with intralesional triamcinolone is a concern, as the need to remove residual premalignant tissue with circumcision after this treatment is unknown.(A1)

Glans resurfacing or reconstruction may be performed using a skin graft from the thigh. Such surgery has been reported to preserve sensation and normal sexual ability postoperatively.[69] 

Meatotomy surgery

This procedure is typically performed with a ventral slit. A straight clamp is placed between the ventral surface of the glans and the inferior urethra to provide initial hemostasis. The clamp is removed after several minutes. Electrocautery may be used for bleeding. The cut edges are closed with small absorbable sutures, usually 000 and 0000. A single, continuous suture is not recommended, as it may cause a purse-string effect.

One technique involves a continuous suture on each meatal lip, which is then reinforced with 1 or more interrupted sutures. Creating a much larger surgical urethral opening than usual (extended meatotomy) or an interposition procedure is usually recommended for patients with BXO, as the meatal orifice tends to close substantially as it heals. A dorsal slit may also need to be performed in some cases. Topical steroid therapy should be continued after meatotomy surgery.[70]

The success of the surgery depends significantly on postoperative care. The routine involves twice-daily manual separation of the meatal lips until the site is healed to prevent the closure of the urethral opening. Patient self-dilation of the meatus is sometimes useful to prevent closure and restenosis.

The median recurrence rate of meatal stenosis 2 years after meatotomy surgery in patients with BXO is 40%.[71] The long-term recurrence rate has been reported to be as high as almost 90%. Up to about 20% of patients with BXO undergoing circumcision ultimately require meatal surgeries.[72] Meatotomy at the time of circumcision does not appear to improve this outcome and may even increase the risk.[73](B2)

Treatment for urethral strictures

About 20% of patients with BXO require procedures for addressing urethral strictures.[74] BXO-related strictures typically start at the meatus and progress proximally. Such strictures are continuous and may extend as far as the proximal urethra. Urethral strictures in patients with BXO tend to be more difficult to manage than strictures from other etiologies due to the progressive fibrotic cutaneous process underlying this condition.[75] 

Treatment is the same as with other types of urethral strictures, but the recurrence rate is higher at almost 90%. Urethral dilation and direct-vision internal urethrotomy surgery are generally less successful in treating urethral stricture disease in patients with BXO.

Genital skin flaps or grafts with single or staged urethroplasties were frequently performed in the past and enjoyed generally good short-term success.[76] However, the recurrence rate was almost 100% after long-term follow-up, so these techniques are no longer recommended.[77][78]

Single-stage urethroplasty using buccal mucosal grafts is now the gold-standard treatment for significant urethral strictures in patients with BXO.[79][80] Single-stage urethroplasties are preferred over the 2-stage technique whenever possible.[81][82]

The buccal mucosa is the preferred graft material for urethroplasties, as genital skin results in a very high late-failure rate in patients monitored for up to 10 years. Lingual and lower lip sources are recommended if buccal mucosa tissue is insufficient.[83] Split-thickness skin grafts from the thighs may also be used but give inferior long-term results when utilized in 2-stage procedures.[84][85][86]

Severe, recurrent, intractable strictures may require a perineal urethrostomy, which is generally preferred over a suprapubic cystostomy.[87] Routine follow-up is needed at least yearly since recurrences are common. Management is reviewed in the companion StatPearls reference review on "Urethral Strictures."

Differential Diagnosis

Contact dermatitis can occur anywhere on the genitalia. Pruritic, erythematous skin lesions arise from direct contact with a particular substance. The affected area can appear as a red rash with cracked skin.[88][89]

Leukoplakia can resemble lichen sclerosus, with both conditions presenting as white, flat plaques. Like BXO, leukoplakia can undergo malignant transformation. Leukoplakia typically results from chronic irritation between the glans and foreskin. Leukoplakia, lichen planus, PeIN, erythroplasia of Queyrat, and scleroderma cannot be reliably differentiated from BXO (lichen sclerosus) without a biopsy. For more information on PeIN and related disorders, see the companion StatPearls reference review, "Penile Cancer and Penile Intraepithelial Neoplasia."

Plasma cell balanitis, or Zoon balanitis, is a benign condition in older men. The condition usually presents as a flat, red plaque that sometimes has associated smaller red marks. The diagnosis requires a biopsy.[90][91]

Psoriasis is a chronic, noncontagious disorder, presenting with scaly, red, pruritic cutaneous patches that can arise anywhere on the body. A high turnover rate of skin cells characterizes this autoimmune condition. Plaques are commonly seen and may appear on the penis.[92]

The most important differentials of BXO include the following:

  • Balanitis circumscripta plasmacellularis
  • Bowen disease of the glans
  • Candida infection
  • Carcinoma in situ 
  • Cellulitis
  • Contact dermatitis 
  • Erythroplasia of Queyrat
  • Fixed drug reaction
  • Infectious balanitis
  • Leukoplakia
  • Lichen planus
  • Penile cancer (squamous, verrucous, and fibrosarcoma)
  • PeIN
  • Pseudoepitheliomatous keratotic and micaceous balanitis
  • Psoriasis
  • Radiation dermatitis
  • Recurrent balanoposthitis
  • Scleroderma 
  • SCC
  • Syphilis
  • Zoon balanitis

A thorough clinical investigation, together with a careful diagnostic examination, can distinguish BXO from mimics and guide treatment.

Prognosis

Penile cancer is an uncommon but dangerous male malignancy with a tumor-specific mortality of 30%. Circumcision may significantly reduce this risk, especially when performed in the neonatal period, as phimosis is an independent risk factor for malignant transformation.[93][94] This potentially devastating diagnosis occurs in up to 15% of BXO cases and takes many years to develop. In contrast, lichen sclerosus of the vulva has a reported 5% estimated risk of progression to SCC.[95]

Untreated chronic inflammation is widely known to raise the risk of penile cancer. BXO carries an increased malignant potential, estimated to be as high as 15% if untreated.[96][97][98] Chronic inflammation results in genetic and epigenetic changes, as well as abnormal cellular homeostasis and cytokine activation, promoting malignant transformation.[99] About 28% to 50% of patients with penile cancer have a history of BXO. Early use of steroid creams can significantly limit disease progression, while early circumcision is curative in many clinical situations.

Complications

The complications of BXO usually arise from late diagnosis and may include disease recurrence, phimosis, paraphimosis, meatal stenosis, progression to penile cancer, urethral strictures, and urinary retention. BXO is widely known to lead to SCC, though this association is generally underappreciated and underestimated.[100]

The following complications were noted in a 10-year retrospective study of patients with BXO:

  • 62.6% had foreskin scarring
  • 47.2% of patients had foreskin and meatus involvement
  • 26.4% had foreskin, glans, and meatus involvement
  • 19.8% of patients needed an additional procedure following their circumcision or meatal dilation

In addition to penile cancer, severe, chronic disease may ultimately cause glans atrophy. Renal failure has also been reported.[101] Early diagnosis and treatment can help prevent the progression of the disease.

Postoperative and Rehabilitation Care

Regular monitoring is essential for patients with BXO. Long-term follow-up is necessary, given the possibility of progression to bothersome urethral stricture disease or penile SCC.

Deterrence and Patient Education

Early diagnosis, proper treatment, and regular follow-up visits are essential to avoid sexual dysfunction, urethral strictures, and penile cancers. Primary care providers or urologists should evaluate patients yearly. Patients should be immediately referred to urology if findings from follow-up exams are concerning for possible disease progression or recurrence.

Patients should be counseled on proper self-genital examination. Individuals prescribed topical steroids for lichen sclerosus must strictly adhere to application schedules. Surgical intervention is warranted when topical steroids fail to correct symptoms. Circumcision has been recommended as a precaution in pediatric patients suspected of having lichen sclerosus.

Enhancing Healthcare Team Outcomes

BXO requires the interprofessional contributions of primary care physicians, pediatricians, nurses, pharmacists, dermatologists, and urologists. Prescription high-potency topical corticosteroids are used for initial therapy in symptomatic patients. Surgery is required in a large percentage of patients who continue to have symptoms despite topical treatment, particularly if they develop phimosis. Circumcision and additional surgical interventions may be necessary.

All healthcare team members should be involved in patient education to dispel misconceptions and provide support. Follow-up with primary care physicians and consulting services is vital to prevent the progression of inflammatory changes to SCC or urinary difficulty from stricture disease.

As BXO involves a particularly intimate area of the male anatomy, and some treatments require prolonged therapy or surgery with extended recovery periods, healthcare team members should be aware of how emotionally sensitive the discussion and management of this condition can be and treat it with professionalism and respect.

Clinicians should counsel patients about signs and symptoms to watch for. Indicators of disease progression warrant a prompt urology consultation. Increased awareness of the optimal treatment of BXO and close coordination among the healthcare team members improve outcomes and quality of life for affected individuals.

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