Background
Lichen sclerosus is a chronic, progressive, sclerosing inflammatory dermatosis of unclear etiology. Most reported lichen sclerosus cases (83%) involve the genitalia. In men, this genital involvement has traditionally been known as balanitis xerotica obliterans (BXO). A more accurate term is male genital or penile lichen sclerosus. The image below shows the condition.
BXO was first described by Stühmer in 1928 as a postcircumcision phenomenon. [1] It may affect the foreskin, glans, frenulum, and meatus or urethra and is responsible for most cases (80-90%) of acquired phimosis. [2]
Balanitis xerotica obliterans (lichen sclerosus). Courtesy of Wilford Hall Medical Center Slide collection.
Yardley et al [3] believe that the prevalence of BXO is greater than previous series have shown and that it may manifest in children at an earlier age than previous series have shown. This belief is based on a study of 422 boys at a median age of 6 years 2 months (range, 3 mo to 16 y), of whom 186 (44.1%) received treatment involving surgery (148 circumcision, 33 preputial adhesiolysis, 5 frenuloplasty). Of the 186 boys, 110 had histological tissue examination; 84.8% of skin samples were pathologic. Specifically, tissue showed chronic inflammation (n = 69; 46.6%), BXO (n = 51; 34.5%), and fibrosis (n = 4; 2.7%).
Related Medscape Drugs & Diseases articles include Lichen Sclerosus et Atrophicus, Balanitis Circumscripta Plasmacellularis, and Balanitis in Emergency Medicine.
Pathophysiology
The etiology of male genital lichen sclerosus is unknown, but it is thought to be multifactorial. Balanitis xerotica obliterans (BXO) has occurred in monozygotic twins, which suggests a genetic basis for the disease in some cases. Human papillomavirus type 6 or type 16 has not been detected in patients with BXO, which strongly suggests that genital papillomaviruses do not have a strong association with BXO. Increased levels of tumor necrosis factor, interferon-gamma, and interleukin 1 have been demonstrated. [4]
Etiology
The etiology of male genital lichen sclerosus (balanitis xerotica obliterans [BXO]) is unknown but is thought to be multifactorial. Several contributing factors are possible, as described below.
Circumcision after age 13 years/uncircumcised state
This may very well be due to the effect known as the isomorphic, or Koebner, phenomenon. The large majority of inflammatory dermatoses of the male genitalia, including lichen sclerosus, occur in uncircumcised or late-circumcised men.
The presence of a foreskin may promote chronic irritation or serve to maintain a friendly environment for an as-yet unidentified infectious agent. Such chronic irritation and subsequent inflammation may initiate the changes noted in lichen sclerosus.
Uncircumcised men have higher incidence of urine pooling between the prepuce and glans penis, whereupon occlusion precipitates a Koebner phenomenon and subsequent inflammation. [5]
Postmicturition dribbling or microincontinence
It has been proposed that postmicturation drippling could be a a contributing factor in the pathogenesis of BXO. In a 2018 study, it was found that 91% of men diagnosed with BXO reported microincontinence, compared with 14% in the control group. [6] It is was also proposed that with the tendency of BXO to spare the anogenital region, the distribution of BXO mirrors the areas subject to urine under occlusion and sparing areas that are shielded from urine by the scrotum.
Hormonal factors
Hormonal influences in the development of lichen sclerosus have long been postulated, mainly in female vulvar lichen sclerosus.
Most studies have concentrated on the role of testosterone in the pathogenesis of vulvar lichen sclerosus. Childhood vulvar lichen sclerosus frequently resolves with the onset of menarche and the related pubertal increase in testosterone production in genital skin; additionally, adults with lichen sclerosus have been found to have decreased serum levels of free testosterone, androstenedione, and dihydrotestosterone compared with control subjects.
The underlying defect may be a problem with the function of the enzyme 5-alpha reductase.
Autoimmune disease
Various autoantibodies (including antinuclear, thyroid antimicrosomal, antigastric parietal cell, anti-adrenal cortex, antismooth muscle, and antimitochondrial antibodies) have been detected in patients with lichen sclerosus.
Vitiligo, thyroid disease, diabetes, and alopecia areata have also been commonly reported in association with lichen sclerosus.
In a study by Farrell et al, [4] IgG autoantibodies to extracellular matrix proteins were found in 80% of lichen sclerosus patients. An association between BXO and the major histocompatibility complex class II antigen HLA-DQ7 has also been found. [7] This region is known to confer increased risk of autoimmune disease such as rheumatoid disease, type 1 diabetes mellitus, and systemic lupus erythematosus.
Genetic factors [8]
Lichen sclerosus (not necessarily genital lichen sclerosus) has been reported in families, including twins (identical and nonidentical), sisters, mothers and daughters, and a brother and sister. Note, however, that no consistent pattern of genetic inheritance has been identified.
Presence of human papillomaviruses
The presence of human papillomaviruses (HPVs) has been reported in some cases of childhood penile lichen sclerosus. Whether the lichen sclerosus is directly attributable to HPV infection, or if lichen sclerosus merely promotes HPV infection is unclear.
Patients with penile lichen sclerosus alone have not been demonstrated to have a higher incidence of HPV infection.
In two studies that included 23 and 11 children, HPV was identified in 52% and 64% of cases, respectively. [9, 10] However, HPV is more common in uncircumcised males, and the finding of HPV infection in such patients could be incidental.
A 2017 systematic review of 27 papers reporting the prevalence of HPV in lichen sclerosus revealed that HPV was present in 22% of lichen sclerosus cases. [11] It also highlighted HPV-16 as the most common genotype.
Other
In a study of 18 patients [12] with combined buccal mucosa grafting and genital skin flap reconstruction of extensive anterior urethral strictures, 16.7% of stricture cases were caused by BXO.
Epidemiology
Frequency
United States
Kizer et al [13] noted that of 153,432 male patients discharged from Brooke Army Medical Center, 108 (0.070%) had a diagnosis of balanitis xerotica obliterans (BXO). The age distribution was similar over a range of 2-90 years, with the exception of the third decade, when the incidence almost doubled. Black and Hispanic patients had twice the rate found in white patients (10.59 cases, 10.67 cases, and 5.07 cases per 10,000 patients, respectively).
International
The prevalence of male genital lichen sclerosus (balanitis xerotica obliterans [BXO]) has traditionally been estimated at 1 case per 300-1000 males. No recent studies confirm this estimate, but male genital lichen sclerosus is not considered a rare condition. Huntley et al [14] reported on 100 consecutive patients seen in pediatric urology clinics who were followed to discharge. Eighteen referrals for circumcision were for religious reasons. Of the other 82 patients, the main reason for referral was retractability or phimosis. Six patients were identified as having BXO, a condition that had not been suggested on referral. Epidemiological data continue to show that BXO can effect boys. [15, 16] Some in Italy claim that the incidence of BXO has been understated. [17]
In Austria, 75 boys younger than 10 years were treated for phimosis; phimosis grade 2 or 3 (schema by Kikiros) was suspected of being BXO. Boys were given either circumcision or conservative therapy with circumcision secondarily (only if therapy did not yield good results in the conservative group). A pathologist examined every circumcision specimen. Doctor performed circumcision primarily in 29 boys and secondarily in 17 boys (mean age, 3.7 y; range, 1-10 y). The pathologist found BXO, chronic inflammation, and normal histological results in 8 (17.4%), 26 (56.5%), and 12 (26.1%) of patients, respectively. The average follow up was approximately 8 months. Doctors did not report recurrences. BXO appeared to be more common than previously reported. The clinical appearance can be confusing in boys, and preoperative BXO suspicion failed to correlate with the final biopsy results. [18]
Race
Male genital lichen sclerosus (balanitis xerotica obliterans [BXO]) has no known predilection for any racial or ethnic group.
Sex
Male genital lichen sclerosus (balanitis xerotica obliterans [BXO]) occurs most frequently in persons who are uncircumcised and who are of middle age. One study [19] revealed that 51 (98%) of 52 patients clinically diagnosed with penile lichen sclerosus were uncircumcised.
Age
Although males with genital lichen sclerosus (balanitis xerotica obliterans [BXO]) are most frequently of middle age, the condition also may appear in children, ranging from young boys to adolescents.
The overall childhood incidence of BXO has been reported to be 5-6%. [20]
In 2019, a 10-year retrospective review of children aged 16 and younger undergoing circumcision revealed that BXO occurred in 91 (8.9%) of 1025 children, mostly in the group aged 5-10 years. [21]
The incidence of BXO in pediatric patients is higher than most physicians realize. Additionally, the incidence of BXO is high in boys with phimosis. [20, 22, 23]
Prognosis
Male genital lichen sclerosus is chronic and often progressive. Regression or improvement of atrophic areas is unexpected.
Malignancies have been reported to arise in penile lichen sclerosus lesions (rare); most common cancers are squamous cell carcinoma (SCC), [24] adenosquamous carcinoma, and verrucous carcinoma. A study of 86 uncircumcised men with genital lichen sclerosus revealed malignant changes (3 SCC, 1 SCC in situ, and 1 verrucous carcinoma) occurring in 5 (5.8%) subjects. The average time between diagnosis of lichen sclerosus and subsequent diagnosis of penile malignancy was 17 years. [25] Notably, 4 of the 5 patients with malignant changes were found by polymerase chain reaction to have evidence of HPV-16 in their tissue specimens. It has been suggested that lichen sclerosus may promote HPV infection and perhaps the development of SCC. [9]
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Balanitis xerotica obliterans (lichen sclerosus). Courtesy of Wilford Hall Medical Center Slide collection.
