BASICS
The International Society for the Study of Vulvar Disease recommends use of the term "lichen sclerosus" (LS) for males and females (1).
DESCRIPTION
- Balanitis xerotica obliterans (BXO) is the historical term for LS affecting the male genitalia, primarily the penis.
- BXO is associated with destructive inflammation, phimosis, urethral stricture disease, and squamous cell carcinoma (SCC). The disease is more common in uncircumcised males, and the diagnosis is confirmed by biopsy. BXO is the male equivalent of LS atrophicus in females.
- There are specific histologic features of LS/BXO.
EPIDEMIOLOGY
- The prevalence is 1 in 300 to 1 in 1,000 men. Peak incidence appears to be 21 to 30 years of age (2).
- Neonatal circumcision appears to prevent development of BXO. However, circumcision later in childhood may not be protective. As a prospective study of 1,178 boys presenting with phimosis who underwent circumcision and histologic analysis of the excised skin, 40% had BXO on circumcision pathology, with those males 9 to 11 years having the highest incidence (3).
- Affects foreskin and glans in 57-100%, meatus in 4-37% with involvement of urethra in about 20% (4)
ETIOLOGY AND PATHOPHYSIOLOGY
- The exact cause of BXO is unknown. Several theories have been proposed to account for male BXO
- Autoimmune theory: One of the most accepted theories is immune dysregulation. Organ-specific antibodies, as well as an increased incidence of other autoimmune conditions such as diabetes mellitus, vitiligo, and alopecia, have been identified in patients with LS (5, 6, 7).
- Infectious: Studies have yielded conflicting results regarding the role of Borrelia in the pathogenesis of LS (8). One study demonstrated an increased incidence of Epstein-Barr virus DNA in vulvar LS than controls (9).
- Local factors: Chronic exposure to urine has been proposed to be a causative factor (10,11).
RISK FACTORS
BXO has a predilection for the warm, moist, urine-exposed environment that exists under the foreskin. Depasquale et al. (4) noted recurrence of BXO when there was redundant skin postcircumcision; recurrence was also common when there were redundant skin folds due to obesity. There appears to be an increased risk for family members to develop LS, suggesting a genetic component to the etiology.
GENERAL PREVENTION
- Neonatal circumcision appears to be protective.
- Early diagnosis may allow for earlier treatment to prevent anatomic changes, such as stricture, and prevent malignant change (1).
- Many advocate that treatment of even asymptomatic patients should occur to prevent disease progression and possible malignancy (1).
- Currently, there is no curative treatment, and long-term follow-up is needed because of the risk of malignancy (8).
COMMONLY ASSOCIATED CONDITIONS
BXO typically occurs in the uncircumcised penis and appears to spare those who underwent newborn circumcision, but circumcision later in childhood does not appear to be protective.
DIAGNOSIS
HISTORY
- Because BXO occurs almost exclusively in uncircumcised males and less commonly in those who underwent a childhood circumcision, a history of circumcision and timing of circumcision should be assessed.
- Assess for the following:
- Ability to retract the foreskin in uncircumcised males
- Meatal stenosis: deflection of urine stream, long thin stream, discomfort with urination
- Urethral stricture: decreased force of stream, straining to void, incomplete emptying (11)
- History of pain, tenderness to touch, or pain with erection (11)
PHYSICAL EXAM
- Early findings are grayish to bluish white discoloration of the glans and/or inner surface of the prepuce.
- Later findings include thinning of the affected skin, sclerotic plaques and tightening, and inability to retract the foreskin (8).
- Fissures may occur with erections and sexual activity.
- Purpura, bullae, erosions, and ulcerations may be noted with later course of disease.
- Phimosis or paraphimosis may be present.
- Meatal involvement may occur with superficial adhesions between the edges or in more extensive disease, with areas of dense white fibrosis.
- In long-standing disease, the penile urethra may feel thickened to palpation due to mucosal involvement and spongiofibrosis. Proximal urethral spread is confluent in nature.
DIFFERENTIAL DIAGNOSIS
Lichen planus, localized scleroderma, leukoplakia, cutaneous rash of Lyme disease, genital herpes, syphilis, fixed drug eruption, vitiligo, Reiter syndrome, SCC, fixed drug eruption, erythroplasia of Queyrat
DIAGNOSTIC TESTS & INTERPRETATION
Diagnostic Procedures/Other
Cutaneous biopsy is helpful to confirm the diagnosis. The affected tissue shows
- Basal cell vacuolization
- Epidermal atrophy, dermal edema
- Collagen homogenization
- Focal perivascular infiltrate of the papillary dermis
- Plugging of the ostia of follicular and eccrine structures (12)
- Pathologic evaluation is also useful to rule out SCC.
- An assay for circulating antibodies to ECM-1 is a possible indicator of disease severity (13).
- Epidermal hyperplasia, epidermotropism of lymphocytes, and basement membrane thickening help identify early LS
- Eosinophils are not uncommon in biopsy specimen in genital LS (14).
TREATMENT
- Currently, there is no curative treatment. The focus of treatment is on limiting skin involvement with disease, relieving symptoms, and preventing anatomic changes such as urethral stricture and malignant change.
- Many advocate treatment of the disease, even in the absence of symptoms, to prevent progression.
- Early treatment may prevent development of severe symptoms and possibly allow patients to avoid surgery (1).
MEDICATION
Nonsurgical approaches are the initial treatment, with surgery reserved for cases of disease progression despite medical therapy.
First Line
- The mainstay initial therapy is steroid therapy. Steroids have been shown to improve the initial symptoms, slow disease progression, and reverse some of the histologic changes seen in BXO. There is no standard treatment recommendation regarding the type of steroid used and the duration of treatment. Steroid therapy is not approved by the FDA for the treatment of BXO. Topical high-potency corticosteroids such as mometasone ointment and clobetasol 0.05% have been used successfully (15,16)[B].
- Possible side effects of topical steroids include cutaneous atrophy, adrenal suppression, hypopigmentation, and contact sensitivity.
- When topical therapy is discontinued, the disease process may resume.
- The macrolide-derived immunomodulator tacrolimus (FK506) has been used with success in lesions involving the glans and penis (17)[B].
- Retinoid acitretin has been used in patients with severe disease resistant to topical steroid (18)[B].
- Photodynamic therapy has been used in women with LS, but trials with men are lacking.
SURGERY/OTHER PROCEDURES
- Surgical treatment is reserved for cases of disease progression and in males with refractory phimosis, meatal stenosis, or urethral stricture.
- Refractory phimosis is best treated with circumcision, which may be challenging if the disease is extensive (11).
- Meatoplasty has been shown to achieve better functional results and provide a more durable treatment for meatal stenosis than a simple meatotomy (19)[C].
- Urethral stricture disease is best treated by excision of the involved urethra and substitution urethroplasty. Currently, buccal mucosa is the preferred tissue, but bladder mucosa may be needed if there is extensive urethral involvement. A staged repair is often used for extensive urethral stricture disease (4)[C].
- In patients with severe disease, it may be appropriate to perform perineal urethrostomy (20,21).
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Due to the risk of development of SCC, even adequately treated patients require long-term follow-up. Some suggest yearly evaluation once the disease has been adequately treated.
PATIENT EDUCATION
Patients treated with steroid therapy must be aware of the risks of steroid therapy as well as the potential for the disease to recur once steroid therapy is discontinued. Furthermore, they must be counseled regarding the long-term risk of SCC and the need for yearly monitoring, with sooner visits if any changes are noted.
PROGNOSIS
There is no curative therapy and thus patients are at risk for recurrence of the disease process. Those with meatal or urethral involvement are at risk for recurrent stricture disease after treatment, and thus, require follow-up.
COMPLICATIONS
See "Treatment" for side effects of steroid therapy. Treatment of meatal stenosis is associated with the risk of recurrent meatal stenosis. Treatment of urethral stricture disease is associated with the risk of recurrent stricture disease, urethrocutaneous fistula, and poor cosmesis.
REFERENCES
11 Stewart L, McCammon K, Metro M, et al. SIU/ICUD consultation on urethral strictures: anterior urethra-lichen sclerosus. Urology. 2014;83(3 Suppl):S27-S30.22 Kizer WS, Prarie T, Morey AF. Balanitis xerotica obliterans: epidemiologic distribution in an equal access health care system. South Med J. 2003;96(1):9-11.33 Kiss A, Kir ¡ly L, Kutasy B, et al. High incidence of balanitis xerotica obliterans in boys with phimosis: prospective 10-year study. Pediatr Dermatol. 2005;22(4):305-308.44 Depasquale I, Park AJ, Bracka A. The treatment of balanitis xerotica obliterans. BJU Int. 2000;86(4):459-465.55 Lipscombe TK, Wayte J, Wojnarowska F, et al. A study of clinical and aetiological factors and possible associations of lichen sclerosus in males. Australas J Dermatol. 1997;38(3):132-136.66 Azurdia RM, Luzzi GA, Byren I, et al. Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease. Br J Dermatol. 1999;140(1):79-83.77 BjekiÄ M, Å ipetiÄ S, MarinkoviÄ J. Risk factors for genital lichen sclerosus in men. Br J Dermatol. 2011;164(2):325-329.88 Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol. 2013;14(1):27-47.99 Aid © S, Lattario FR, Almeida G, et al. Epstein-Barr virus and human papillomavirus infection in vulvar lichen sclerosus. J Low Genit Tract Dis. 2010;14(4):319-322.1010 Bunker CB, Edmonds E, Hawkins D, et al. Re: lichen sclerosus: review of the literature and current recommendations for management: Pugliese J. M., Morey A. F. and Peterson A. C. J Urol 2007;178:2268-2276. J Urol. 2009;181(3):1502-1503.1111 Edmonds EV, Hunt S, Hawkins D, et al. Clinical parameters in male genital lichen sclerosus: a case series of 329 patients. J Eur Acad Dermatol Venereol. 2012;26(6):730-737.1212 Link RE. Cutaneous diseases of the external genitalia. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:443-444.1313 Oyama N, Chan I, Neill SM, et al. Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus. J Clin Invest. 2004;113(11):1550-1559.1414 Lester EB, Swick BL. Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding. J Cutan Pathol. 2015;42(1):16-21.1515 Dahlman-Ghozlan K, Hedblad MA, von Krogh G. Penile lichen sclerosus et atrophicus treated with clobetasol dipropionate 0.05% cream: a retrospective clinical and histopathological study. J Am Acad Dermatol. 1999;40(3):451-457.1616 Val I, Almeida G. An overview of lichen sclerosus. Clin Obstet Gynecol. 2005;48(4):808-817.1717 Hengge UR, Krause W, Hofmann H, et al. Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus. Br J Dermatol. 2006;155(5):1021-1028.1818 Ioannides D, Lazaridou E, Apalla Z, et al. Acitretin for severe lichen sclerosus of male genitalia: a randomized, placebo controlled study. J Urol. 2010;183(4):1395-1399.1919 Morey AF, Lin HC, DeRosa CA, et al. Fossa navicularis reconstruction: impact of stricture length on outcomes and assessment of extended meatotomy (first stage Johanson) maneuver. J Urol. 2007;177(1):184-187.2020 Kulkarni S, Barbagli G, Kirpekar D, et al. Lichen sclerosus of the male genitalia and urethra: surgical options and results in a multicenter international experience with 215 patients. Eur Urol. 2009;55(4):945-954.2121 Peterson AC, Palminteri E, Lazzeri M, et al. Heroic measures may not always be justified in extensive urethral stricture due to lichen sclerosus (balanitis xerotica obliterans). Urology. 2004;64(3):565-568.
ADDITIONAL READING
- Chi CC, Kirtschig G, Baldo M, et al. Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol. 2012;67(2):305-312.
- Garaffa G, Shabbir M, Christopher N, et al. The surgical management of lichen sclerosus of the glans penis: our experience and review of the literature. J Sex Med. 2011;8(4):1246-1253.
- Jayakumar S, Antao B, Bevington O, et al. Balanitis xerotica obliterans in children and its incidence under the age of 5 years. J Pediatr Urol. 2012;8(3):272-275.
- Neuhaus IM, Skidmore RA. Balanitis xerotica obliterans and its differential diagnosis. J Am Board Fam Pract. 1999;12(6):473-476.
- Pandher BS, Rustin MH, Kaisary AV. Treatment of balanitis xerotica obliterans with topical tacrolimus. J Urol. 2003;170(3):923.
- Powell JJ, Wojnarowska F. Lichen sclerosus. Lancet. 1999;353(9166):1777-1783.
- Riddell L, Edwards A, Sherrard J. Clinical features of lichen sclerosus in men attending a department of genitourinary medicine. Sex Transm Infect. 2000;76(4):311-313.
CODES
ICD10
N48.0 Leukoplakia of penis
ICD9
- 607.81 Balanitis xerotica obliterans
- 607.0 Leukoplakia of penis
SNOMED
- Balanitis xerotica obliterans
- Lichen sclerosus of penis (disorder)
CLINICAL PEARLS
- BXO is the male equivalent of LS atrophicus in females.
- Treatment is aimed at the relief of symptoms and prevention of disease progression.
- Topical steroid therapy is the first-line therapy in early stages of the disease.
- Diagnosis is made by cutaneous biopsy.