Sandbox:Balanitis xerotica obliterans

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Vishal Devarkonda, M.B.B.S[2]

Synonyms and keywords:BXO, Penile lichen sclerosus

Overview

Balanitis xerotica obliterans (BXO) is a dermatological (skin) condition affecting the male genitalia. It was first described by Stuhmer in 1928, though earlier reports describe what may have been the same condition.[1] BXO commonly occurs on the foreskin and glans penis.[2] Atrophic white patches appear on the affected area,[3] and commonly, a whitish ring of indurated (hardened) tissue usually forms near the tip that may prevent retraction.[2]

Classification

There is no established classification system for BXO.

Pathophysiology

The exact etiology of BXO is unknown, but multiple factors are considered to play an important in the development of BXO.

Factors associated with pathogenesis of BXO
Uncircumcised Penis	Accumulation of secretions and epithelial debris between the foreskin and coronal sulcus leads to chronic irritation, sublincal trauma.
Autoimmune diseases	Patients with BXO, were found to have an other associated autoimmune conditions, which include: diabetes mellitus, vitiligo, alopecia aerata. Some studies have showned association between BXO and HLA DQ7 with DR11 and DR12.
Infections	Human papillomavirus (HPV)	Several studies have implicated human papillomavirus as a causative agent in pathogenesis of BXO. HPV 16, 18, 33 and 51 have been found to associated with BXO. Recent studies reported lack of clincal correlation of BXO and HPV, has they both have unrelated transcriptosome.
	Several studies have reported association of various infectious organisms with development of Balanitis xerotica obliterans, which include: Borrelia burgdoferi HCV Epstein-Barr virus
Genetics	Several studies have proposed genetic association and lichen sclerosis. In females, 12% of patients were found to have a family history of lichen sclerosis,. In males, there is no evidence familial predisposition.
Environmental factors		BXO is known to demonstrate koebner phenomenon. Trauma, old scars, skin grafts, sunburn and radiation were found to be associated with BXO. Some studies have proposed that post-micturation dribbling or microincontinence plays a central role in development of BXO.

Histopathology

Histopatholgy findings found in BXO include:

Early stage of BXO

• Moderately heavy lymphocytic infiltrate in found in basal epidermis and superficial dermis in early stages of the lesion.

Late stages of BXO

• Epidermis becomes atrophic with surface hyperkeratosis, thickened basement membrane
• Broad zone of subepidermal oedema with homogenization of collagen, which becomes more sclerotic over time.
• In few cases, epidermis is detached from dermis resulting in formation of haemorrhagic bullae.
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Causes

The etiology of BXO is uncertain. However, some possibilities have been suggested:

Causes of BXO
Uncircumcised Penis

Epidemiology and Demographics

The true prevalence of BXO is controversial and unclear. One study calculated a rate of 0.6% of boys affected by their 15th birthday. Another reported a rate of 0.07%. However, a review noted that "with a high degree of suspicion and histologic examination, the condition will prove to be much more frequent than one generally believes." Another suggested that "more cases would be diagnosed during infancy if all dried foreskin were examined systematically." Another remarked that the condition "may be misdiagnosed or ignored in the young boy." Yet another commented that "its true incidence is not appreciated because most cases are cured by circumcision, and unfortunately many surgeons still fail to send their circumcision specimens for histology." Another remarked that the "extent of asymptomatic disease in this series would suggest the true prevalence of LS in men might be much higher than published work suggests."

According to some authors, the disease most frequently affects middle-aged men. However, a large study reported that the age distribution was similar from 2 to 90 years of age, except for men in their twenties, who were at twice the risk. The same study found that black and Hispanic men had approximately twice the risk of white men. The authors suggested possible reasons for this, including access to health care, differences in neonatal circumcision rates, and climate differences.

Mallon et al. found that BXO was related to circumcision status. Adjusting for age, lack of circumcision was associated with an odds ratio of 53.55. The finding was statistically significant. However, BXO has also been noted to occur after late circumcision, especially when performed for phimosis.

Screening

There is no established screening guidelines for BXO.

Natural History, Complications, and Prognosis

Natural history

If left untreated, there is risk for malignant transformation.

Complications

Complication of BXO include the following:

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.

Prognosis

BXO is chronic and often progressive. Please see the following section on treatment.

The condition may cause pain, irritation, and disturbance of sexual function.

In later stages, a meatal stricture may occur, causing urinary retention. This may result in bladder or kidney damage.

The coronal sulcus and frenulum may be destroyed.

Phimosis or paraphimosis may occur.

Several studies indicate that BXO may play a pre-cancerous role, resulting in squamous cell carcinoma of the penis, a form of penile cancer.

Prognosis is good with treatment.

Diagnosis

Neuhaus and Skidmore report that "Tzanck smear and cutaneous biopsy, along with a rapid protein reagin test, will provide a definitive diagnosis."

Depasquale et al. note that many surgeons do not send circumcision specimens for histology. They caution that this practice "is becoming medicolegally indefensible in a litigation-conscious society, where the clinical sequelae of BXO are often misinterpreted by the patient as surgical errors."

History and symptoms

Patients with Zoon balanitits could be asymptomatic or present with:

• Itching (pruritus) of the genitalia.
• Discomfort in urination(dysuria)
• Pain in the gential region
• blood stain discharge
• Difficult or painful sexual intercourse

Physical examination

Physical examination findings include:

• Well circumscribed single or multiple, orange-red in colour with a characteristic glazed appearance and multiple pinpoint redder spots-"cayenne pepper spots"(please click here to view the image) most commonly involving the glans penis, but inner surface of prepuce and coronal sulcus may be involved.
• Though uncommon, lesions of Zoon balanitis can involve other sites which include labia minora in females, oral mucosa, conjunctiva, urethra, cheeks, and epiglottis have been described in literature.

Clinical criteria in diagnosing Zoon balanitis
Shiny, erythematous patches on the glans, prepuce, or both
Lesion present for > 3months
Absence of lesion suggestive of Lichen planus, psoriasis elsewhere on the body
Poor response to topical therapies
Absence of concurrent infections which are ruled out after performing tzanck, potassium hydroxide, gram stain, and VDRL test.

Laboratory findings

Reflectance confocal microscopy	A nucleated honeycomb pattern and vermicular vessels is a clue for benign inflammatory genital skin disease
Dermoscopy	Focal/diffuse orange-yellowish structure, less areas representing hemosiderin deposition, curved vessels due to epidermal thinning helps in distinguishing ZB from carcinoma in situ.

Treatment

Therapy focuses on prevention of disease progression.[30]

Shelley reported some success with long-term antibiotic therapy. However, relapses were seen upon stopping treatment.[31]

Some success has been reported with topical steroids,[32] when scarring is minimal,[33] though some have found this ineffectual.[34]

Moderate therapeutic results have been reported using etretinate.[35]

Some success has been reported in the use of carbon dioxide laser therapy.[36][37]

Many authors report that circumcision is the treatment of choice,[9][2][38] with modifications if necessary.[39] Pasieczny suggests testosterone ointment, however.[40]

Glansectomy may be required.[9]

Currently, topical steriods are the most commonly used and most effective medication for the treatment of the adverse skin changes associated with BXO. Patients with urethral stricture disease associated with BXO are generally best managed with surgery to relieve the obstruction. Although urethral dilation is a treatment option, this treatment generally offers only temporary relief of the blockage and a complication of dilations can be stricture progression. The best treatment of urethral stricture treatment options are extended meatotomy (an open incision of the urethra) for short strictures and staged tissue transfer urethroplasty, a surgery to reconstruct the urethra using grafts such as buccal mucosa from inside the cheek.

General measures

Good hygiene which include retracting the foreskin regularly and gentle cleansing of entire glans, preputial sac, and foreskin were found effective in treating the diseases.

Medical Therapy

Medical therapy for BXO include:

Various medical managements for BXO
	Drug dosage	Effectiveness
Topical steroids	Betamethasone diproprionate 0.05% or or clobetasol proprionate 0.05% cream or ointment once or twice daily After 6–8 weeks, reduce the application of the topical steroid to every second day After 12–16 weeks to assess response to treatment(mometasone aceponate 0.1% cream can be substituted if there is a good response) No improvement by 6 months, then use of the potent topical steroid should be abandoned.	3 out of 6 patients responded
Topical calineurin inhibitors	Tacrolimus ointment 0.1% twice daily	Shouldn't be used as first-line therapy
	Pimecrolimus cream 1% twice daily
Tricyclic antidepressant or gabapentin.	Can be used in cases when BOX is associated with penile dysaesthesia.
			Surgery
Surgical treatment often involves circumcision. Trial of steroids is usually prescribed before subjecting patients for surgery. Phimosis is an indication for surgery. In patients with severe BXO may require an extensive surgery with disease control, function and cosmesis in carefully balanced. Some cases may require meatoplasty, extensive urethroplasty and reconstructions. Patients who undergo surgery should be follow up as the disease as tendency to recur.(BOX as high tendency to recur due to koebner phenomenon) Patients should be advice for regular testicular self-examination and should be advice to return if the lesion revur.
Prospective therapies
Intralesional corticosteroids, topical and intramuscular testosterone, intravenous procaine, topical oestrogen and retinoid creams, oral vitamin E, radiation therapy and CO2 laser are currently been studies for there role in treating BOX

<section></section>Prevention

There is no known means of preventing BXO. However, one study reports that the data "suggest that circumcision prevents or protects against common infective penile dermatoses."

Primary Prevention

Circumcision in males can help in reducing risk of having ZB.

Secondary prevention

There is no secondary prevention measures.

References

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