| Abstract|| |
Male genital lichen sclerosus (MGLSc) is a chronic inflammatory skin disease responsible for male sexual dyspareunia and urological morbidity. An afeared complication is squamous cell carcinoma (SCC) of the penis. The precise etiopathogenesis of MGLSc remains controversial although genetic, autoimmune and infective (such as human papillomavirus (HPV) hepatitis C (HCV), Epstein-Barr virus (EBV) and Borrelia) factors have been implicated: Consideration of all the evidence suggests that chronic exposure of susceptible epithelium to urinary occlusion by the foreskin seems the most likely pathomechanism. The mainstay of treatment is topical ultrapotent corticosteroid therapy. Surgery is indicated for cases unresponsive to topical corticosteroid therapy, phimosis, meatal stenosis, urethral stricture, carcinoma in situ (CIS) and squamous cell carcinoma.
Keywords: Male genital lichen sclerosus, etiology, pathogenesis, management
|How to cite this article:|
Bunker CB, Shim TN. Male genital lichen sclerosus. Indian J Dermatol 2015;60:111-7
What was known?
MGLSc is a cause of male sexual dysfunction and urological morbidity and associated with squamous carcinoma of the penis. It has been held to be an autoimmune disease.
| Introduction|| |
MGLSc is an acquired, chronic inflammatory cutaneous disease of disputed etiology. It causes acute and chronic balanoposthitis and scarring that can result in significant sexual and urinary dysfunction as well as conferring a risk of squamous carcinoma of the penis. ,
The exact incidence and prevalence are difficult to ascertain. This could be because it is managed by many specialties (dermatology, genito-urinary medicine, urology and pediatrics), as well as significant under-recognition and hence under-reporting by patients and physicians. The estimated incidence of LSc ranges from 1/300 (0.3%) to 1/1000 (0.1%) in both sexes.  A more recent study reported the incidence of MGLSc of 1.4 patients per 100, 000 visit.  The epidemiology may vary between countries and racial groups because MGLSc is principally a disease of the uncircumcised although it can persist or recur after circumcision. There is a bimodal age incidence with peaks in young boys and in adult men, late in the fourth decade. ,,,,
MGLSc can be the cause of significant morbidity. The symptomatology is an expression of preputial and urethral dysfunction very often summarized as male dyspareunia. ,, The spectrum of presentation is wide. It may be asymptomatic. Some patients describe spontaneous itching, burning, bleeding, tearing, splitting (of the prepuce and frenulum), or hemorrhagic blisters or urinary problems such as dysuria and narrowing of the urinary stream, or anatomical changes of the genitalia. Most men (55%) have symptoms associated with sexual activity but dyspareunia may be even more common than this statistic due to failure or difficulty in eliciting the symptomatology.  Other presentations are non-retractile foreskin (phimosis), foreskin fixed in retraction (paraphimosis), urethritis, urethral stricture, urinary retention and renal failure. Some cases are diagnosed at the presentation of CIS or frank SCC. The disease and its complications have a significant impact on male sexual health. ,
Signs may be subtle or florid. The organ should be examined systematically and sedulously, including with a hand lens. The classical genital morphologic manifestations of MGLSc are similar to those features of the disease encountered at extragenital sites, and include atrophic ivory-white patches (leukoderma) or plaques, hypertrophic, slightly scaly patches or plaques with telangiectasia and sparse purpura. A constrictive lichenoid posthitis is commonly seen associated with a fibrotic preputial band causing "hourglass" "waisting" of the penile shaft. Variable asymmetric, sometimes florid, Zoonoid inflammation may be present and distract the clinician from the correct diagnosis. The glans may be etiolated, affected by sclerosis especially parameatally and show purpura, ecchymosis or angiokeratomas. Meatal involvement may be subtle with encroachment and blunting of the architecture or more overt with "pin hole" narrowing of the meatus, but may be more overt and extensive. Adhesions occur and can be subcoronal or transcoronal. Anatomical definition is lost with effacement of the coronal sulcus and early penile papules. The frenulum is a particular target manifesting sclerosis or complete obliteration of the frenulum. ,, Perianal involvement with MGLSc in men is very rare. , Concomitant extragenital LSc is also extremely rare (<0.1%). ,
| Etiology|| |
Genetic factors have been proposed on the basis on reports of familial cases and association with HLA antigens. Familial LSc has been observed in identical and non-identical twins, sisters, mothers and daughters. , Family history was found in 12% of female genital (FG) LSc.  However, there is little evidence of a familial predisposition to LSc in boys. , The human leukocyte antigen (HLA) complex is known to determine an individual's susceptibility to inflammatory diseases by influencing both cellular and humoral immunity. Majority of this work involved women. Several studies have found HLA DQ7 and, to a lesser extent, HLA DQ8 and DQ9 to be more common in FG LSc than in controls,  especially if the onset of LSc is in childhood.  HLA-B*08, B*18, -B*15, B*57, -CW*03, -CW*07, CW*18, -DQ3, -DQ7, -DRB1*04, -DRB*4, -DRB1*07, -DRB1*12 and the haplotypes HLA-DRB1*12, -DQB1*03:01/04/09/010 were found to increase susceptibility to FG LSc, whereas HLA-DR17, -DRB1*03:01/04 and the haplotypes HLA-DRB1*03, -DQB1*02, -DRB1*03:01, DQB1*02:01/02/03 appear to protect against (FG) LSc. ,, Increased frequencies of HLA-DR11, -DR12 and DQ7 have been reported in MGLSc. 
GLSc has been associated with atopic eczema in boys.  Filaggrin (FLG) is a key protein that facilitates terminal differentiation of the epidermis and formation of the epithelial barrier, and mutations have been found to be present in atopic dermatitis. A barrier defect due to FLG mutations might contribute to the susceptibility of genital epithelium to urinary irritation in MGLSc.  However, no significant differences were found in a study of 93 MGLSc with the most prevalent filaggrin loss-of-function mutations (R501X, 2282del4, R2447X and S3247X). 
It remains debatable whether autoimmunity underlies this condition. A personal and/or family history of autoimmunity has been shown to be associated with LSc. Organ-specific antibodies such as anti-thyroid, gastric (parietal-cell) tissue, intrinsic factor, antinuclear and anti-smooth muscle autoantibodies have been found in patients with LSc. Autoimmune conditions such as thyroid disease, diabetes, vitiligo, alopecia areata, pernicious anemia, scleroderma and rheumatoid arthritis have been reported in patients with LSc. ,,,,, The similarities of some clinical and histopathological features in LSc and lipoid proteinosis, a rare autosomal recessive genodermatosis associated with pathogenic loss-of-function mutations in the extracellular matrix protein 1 (ECM1) gene, has led to the hypothesis that ECM1 autoimmunity might contribute to the etiopathogenesis of LSc. , Further study suggested although autoantibodies to ECM1 have been found in both FG- and MGLSc, but this may be an epiphenomenon. , Similar conclusion has also been drawn for the role of circulating anti 180NC 16a and anti-BP230 autoantibodies because the percentage of patients with positive circulating anti-BP 180 antibodies appears not to exceed the number found in general population. , It has been proposed there might be different pathogenetic background in male and female patients with preponderance of the role of autoimmunity in (FG) LSc.  Furthermore, different percentages of CD4+ and FOXP3+ lymphocytes were observed in (FG)- and MGLSc suggesting a different pathogenetic pathway. 
(i) Acid-fast bacilli and spirochates
Previous studies have linked several infective agents with LSc. These include acid-fast bacilli and spirochetes. ,,
(ii) Borrelia burgdorferi
0 Acrodermatitis chronica atrophicans caused by Borrelia burgdorferi has some clinical and histological similarities with LSc. Many studies to date have produced conflicting results, which could be due to regional variations in Borrelia burgdorferi and different experimental technique used. , Such an association has been negated. 
Human papillomavirus (HPV) infection has been implicated as a causative agent. A variety of HPV sub-types such as HPV 16, 18, 33 and 51 have been reported in MGLSc.  It remains debatable whether some of these HPV are merely skin surface "passenger HPV" or "driver HPV" that are implicated in the pathogenesis of MGLSc. p16 INK4a can be used as a surrogate biomarker to confirm the diagnosis of HPV-infected penile lesions. ,,, Recent evidence has shown that there is a lack of clinical correlation of MGLSc with HPV and MGLSc has an HPV-unrelated transcriptosome, , endorsing the view that HPV might be an innocent bystander.  Another study has shown that there was no difference in prevalence of MGLSc between HPV-positive and -negative samples.  HPV has also shown to be absent from the foreskin of boys circumcised for persistent phimosis after their first year of life and that topical glucorcorticoid treatment failure is not associated with HPV or any specific histopathological changes.  However, strong immunostaining for p16 INK4a correlated with HPV16/18 infection in 6 out of 18 cases of MGLSc has been reported.  A larger study is required to examine this association. Recent work has shown that there is no correlation of MGLSc (n = 62; HPV positivity = 37.9%) with p16 INK4a immunostaining (P = 0.53) suggesting the detection of skin surface "passenger HPV" and it is unlikely to play a role in the etiopathogensis of MGLSc. 
HCV has been implicated by case reports , but a recent study from our group (n = 61) showed that not one patient with MGLSc had HCV suggesting that it is highly unlikely to play a pathogenic role in MGLSc. 
Epstein-Barr virus (EBV) DNA has been found in 26.5% of 34 vulvar biopsies with FGLS compared with 0% in controls  but its role in MGLSc is not known.
LSc demonstrates the Koebner phenomenon. It arises from areas that have undergone trauma, in old scars (e.g. after vulvectomy and circumcision), on skin grafts, at sites prone to constant friction, and after sunburn or radiation treatment. ,,,,,
Exposure to urine
MGLSc is unequivocally a disease of the uncircumcised male.  MGLSc is exceedingly rare in the male circumcised at birth indicating that the foreskin must play an obligate role in the etiopathogenesis of MGLSc. However, MGLSc does occur in the circumcised male: with hypospadias, with genital jewelry (piercing) after surgery, trauma and instrumentation and in the bariatric patient. It does recur in grafts especially skin grafts more than mucosal grafts. ,,,
Post-micturition dribbling or microincontinence has been proposed to play a central role in the etiopathogenesis of MGLSc. ,,,, Many men presenting with MGLSc confess to dribbling post-micturition. A recent study by our group has shown that 91-100% men with MGLSc have dribbling compared to 14% controls implicating the role of post-micturition microincontinence in MGLSc.  Furthermore, MGLSc patients are often found to have an abnormal urethral meatus or navicular fossa on meticulous examination. In the circumcised male, a tiny drop of urine appearing at the meatus post-micturition will have negligible contact with a keratinized glans before being absorbed by undergarments. In an uncircumcised male, with a similarly dysfunctional terminal urethral apparatus, the situation is very different. In men, dribbled urine, consequent upon post micturition microincontinence, is likely to pool and become occluded between the inner prepuce and distal penis/glans, affecting the frenulum, perimeatal glans and visceral prepuce. Occlusion and the phenomenon of koebnerization precipitate inflammation; inflammation progresses to sclerosis. ,,,, The urinary hypothesis is also supported by the observation of LSc occurring around perineal urethrostomies in patients who undergone perineal urethroplasty for long urethral strictures or severely scarred urethral plate. Chronic intermittent leakage of urine from the perineal urethrostomy following voiding is inevitably occluded between juxtaposed perineal folds with identical pathological consequences in the affected skin to the penile situation described above.  This hypothesis is strengthened by the occurrence of extragenital LSc in the peristomal skin in urostomy patients likely due to occlusion and urine contact. 
Whether MGLSc is a non-specific pathological response to urinary exposure or there is some specific mechanism or culpable constituent of urine remains unknown. Magnetic resonance spectroscopy study suggests that there is not one single indictable component of urine. 
A small study has shown an inverse relationship between the presence of vulval LS and use of beta-blockers and ACE inhibitors. ACE inhibitors may diminish the LSc inflammatory process and therefore protect from LSc. Beta-blockers block cyclic AMP level resulting in upregulation of keratinocyte proliferation, reduced differentiation and increased motility of lymphocytes, which may influence the clinical expression of patients with LSc.  The role of drugs in the causation of MGLSc is not known.
(ii) Metabolic disease
A recent case-controlled study suggested that there might be a metabolic or lifestyle component in the etiology of MGLSc. Increased rates of elevated body mass index, diabetes mellitus, coronary artery disease (CAD) and smoking were observed in MGLSc compared to control group. , Diabetes mellitus and CAD are known to be associated with microvascular disease systematically, and the authors suggested an association of LSc with direct vascular compromise.  However, obese men are frequently seen with GLSc, including those where suprapubic obesity and retraction of the penis (the "vanishing penis") into the pubic mound create a pseudo or neo foreskin in males circumcised at birth or later.
MGLSc and SCC
The risk of transformation of MGLSc to carcinoma in situ (CIS) is difficult to quantify. Early microinvasive disease might be challenging to diagnose clinically against a background of LSc. A retrospective review by Barbagli et al. of 130 patients with MGLSc, revealed 11 men (8.4%) with premalignant or malignant features (7 cases with SCC, 2 cases with verrucous carcinoma, 1 case of SCC associated with verrucous carcinoma and 1 case of erythroplasia of Queyrat).  The time interval between diagnosis of LSc and the development of SCC was 14-30 years. Two forms of penile intraepithelial neoplasia (PeIN) have been described (analogy with the vulvar intraepithelial neoplasia classification): Differentiated PeIN which is often associated with MGLSc and undifferentiated or Bowenoid PeIN which is associated with HPV infection. 
The association of GLSc and SCC is widely recognized and the risk has been estimated at between 2% and 12.5%. ,,,, MGLSc is also considered one of the two pathways for the development of CIS and penile cancer, the other being via HPV infection. , However, in a large series of patients from our clinics not one patient developed SCC, suggesting that accurate diagnosis and definitive curative management are central to arresting carcinogenic drive.
MGLSc and melanocytic lesions
Atypical genital melanocytic naevus has been reported concomitantly in patients with FG- and MGLSc. ,, Cases of melanoma complicating FGLSc have appeared in the literature. ,,,, We have seen three in MGLSc.  It has been postulated that LSc might be an immune response possibly triggered by the melanocytic lesion, alternatively that the inflammatory environment of LSc provides a microenvironmental niche promoting melanocytic neoplasia.
| Diagnosis and Treatment|| |
Most cases of MGLSc can be diagnosed clinically. Under some circumstances a biopsy can be performed. A biopsy is useful to exclude neoplastic transformation and differentiate LSc from erosive lichen planus, scarring cicatricial pemphigoid and lichen simplex. , The histology of LSc is characterized by flattening of the epidermis with variable hyperkeratosis, hydropic degeneration of basal cells and an inflammatory cell dermal infiltrate. However, biopsy histology of MGLSc may be non-specific, depending on timing, site and severity.  A biopsy of the most clinically abnormal area, for example, of inflammation or scarring, may not yield a histological diagnosis. There may be nonspecific inflammatory changes (e.g. zoonoid) leading to an erroneous diagnosis of Zoon's balanitis. In many men the preputial or glanular changes may be secondary and reactive to the balanopreputial dysfunction created by the principal proximate or adjacent or apposed site of the LSc. A negative biopsy does not exclude LSc. A negative biopsy does not exclude neoplasia. ,,,
The treatment of MGLSc aims to achieve optimal symptomatic relief, prevention of further deterioration of anatomical architecture changes and a theoretical mitigation of malignant transformation. Our understanding of the role of occlusional contact with urine in the pathogenesis is fundamental to the effective management and the prognosis of MGLSc. ,
Treatment protocols in GLSc are well-established (level evidence III). ,,, Avoidance of contact with soap and urine are essential. Regular use of skin barrier emollient should be instituted. Short, trimmed pubic hair is recommended to avoid hair trapping between the foreskin and the glans penis and hence minimize irritation, abrasion and consequent inflammation.  Early aggressive treatment may prevent disease progression.  An ultrapotent topical corticosteroid (usually clobetasol propionate (level evidence I)) used under supervision for a finite course is effective ,,, and usually problem free, but herpes simplex and wart reactivation do occur. , prophylactic aciclovir should be prescribed for patients with a history of genital HSV. Most men achieved remission by ultrapotent topical corticosteroid (50-60%).  Topical calcineurin inhibitors should not be used in MGLSc because of a theoretical synergistic risk of SCC. ,,, If maximal conventional medical treatment is not possible or fails then circumcision is recommended. Removal of the foreskin alters the local environment of glans penis: It removes the occlusive and koebnerizing effects of the foreskin and hence mitigates the consequences of post-micturition microincontinence. Circumcision is curatively effective in the majority (at least > 75% but precise long term follow up data are lacking).  Some men might require advanced urethromeatal surgery. Our results show that accurate diagnosis and rational management restores sexual function and mitigates the risk of urinary dysfunction and can conserve the foreskin in about 50%. Furthermore, not one patient of the many hundreds of patients seen in the clinic over 20 years has yet developed penis cancer. 
| Conclusion|| |
MGLSc is an acquired, chronic, inflammatory and fibrosing cutaneous disease responsible for significant sexual and urological dysfunction as well as creating a risk of squamous carcinoma of the penis. The etiology of MGLSc is now much better understood. It is not primarily an autoimmune condition. It is likely that an interaction between the irritant effects of urine and other pathogenic factors, such as chronicity, occlusion and as yet undetermined differential epithelial susceptibility, or reaction, to injury, are necessary for the development of MGLSc. Better understanding the pathogenesis of MGLSc is important to minimize sexual morbidity, urological dysfunction, mitigate the cancer risk it generates and preserve the foreskin when possible.
| References|| |
Bunker CB. Male genital skin disease. London: Saunders; 2004.
Bunker CB, Porter WM. Male genital dermatology. In: Rook's Textbook of Dermatology. 9 th
ed. New York: Wiley-Blackwell; 2015 [In Press].
Wallace HJ. Lichen sclerosus et atrophicus. Trans St John's Dermatol Soc (England) 1971;57:9-30.
Nelson DM, Peterson AC. Lichen sclerosus: Epidemiological distribution in an equal access health care system. J Urol 2011;185:522-5.
Lipscombe TK, Wayte J, Wojnarowska F, Marren P, Luzzi, G. A study of clinical and aetiological factors and possible associations of lichen sclerosus in males. Australas J Dermatol 1997;38:132-6.
Edmonds EV, Hunt S, Hawkins D, Dinneen M, Francis N, Bunker CB. Clinical parameters in male genital lichen sclerosus: A case series of 329 patients. J Eur Acad Dermatol Venereol 2012;26:730-7.
Mattioli G, Repetto P, Carlini C, Granata C, Gambini C, Jasonni V. Lichen sclerosus et atrophicus in children with phimosis and hypospadias. Pediatric Surg Int 2002;18:273-5.
Kyriakis KP, Emmanuelides S, Terzoudi S, Palamaras I, Damoulaki E, Ecangelous G. Gender and age prevalence distributions of morphoea en plaque and anogenital lichen sclerosus. J Eur Acad Dermatol Venereol 2007;21:825-6.
Bunker CB. Male genital dermatology. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 8 th
ed. New York: The McGraw-Hill Companies; 2011.
Kantere D, Löwhagen GB, Alvengren F, Månesköld A, Gillstedt M, Tunbäck P. The clinical spectrum of lichen sclerosus in male patients-a retrospective study. Acta Derm Venereol 2014;94(5):542-6.
Sherman V, McPherson T, Baldo M, Salim A, Gao XH, Wojnarowska F. The high rate of familial lichen sclerosus suggest a genetic contribution: An observation cohort study. J Eur Acad Dermatol Venereol 2010;24:1031-4.
Aslanian FM, Marques MT, Matos HJ, Pontes LF, Porto LC, Azevedo LM, et al
. HLA markers in familial lichen sclerosus. J Dtsch Dermatol Ges 2006;4:842-7.
Depasquale I, Park AJ, Bracka A. The treatment of balanitis xeroticca obliterans. BJU Int 2000;86:459-65.
Marren P, Yell J, Charnock FM, Bunce M, Welsh K, Wojnarowska F. The association between lichen sclerosus and antigens of the HLA system. Br J Dermatol 1995;132:197-203.
Powell J, Wojnarowska F, Winsey S, Marre P, Welsh K. Lichen sclerosus premenarche: Autoimmunity and immunogenetics. Br J Dermatol 2000;142:481-4.
Gao XH, Barnardo MC, Winsey S, Ahmad T, Cook J, Agudelo JD, et al
. The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus. J Invest Dermatol 2005;125:895-9.
Sentürk N, Aydin F, Birinci A, Yildiz L, Cantürk, Durupinar B, et al
. Coexistence of HLA-B*08 and HLA-B*18 in four siblings with lichen sclerosus. Dermatology 2004;208:64-6.
Azurdia RM, Luzzi GA, Byren I, Welsh K, Wojnarowska F, Marren P, et al
. Lichen sclerosus in adult men: A study of HLA associations and susceptibility to autoimmune disease. Br J Dermatol 1999;140:79-83.
Becker K, Meissner V, Farwick W, Bauer R, Gaiser MR. Lichen sclerosus and atopy in boys: Coincidence or correlation? Br J Dermatol 2013;168:362-6.
Bunker CB. Atopy, the barrier, urine and genital lichen sclerosus. Br J Dermatol 2013;169:953.
Shim TN, Brown SJ, Campbell LE, Francis N, Dinneen M, Hawkins D, et al
. Male genital lichen sclerosus and filaggrin. Br J Dermatol 2014;171(Suppl 1):35.
Meyrick Thomas RH, Ridley CM, McGibbon DH, Black MM. Lichen sclerosus et atrophicus and autoimmunity - A study of 350 women. Br J Dermatol 1988;118:41-6.
Cooper SM, Ali I, Baldo M. Wojnarowska F. The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: A case-control study. Arch of Dermatol 2008;144:1432-5.
Lutz V, Francès C, Bessis D, Cosnes A, Kluger N, Godet J, et al
. High frequency of genital lichen sclerosus in a prospective series of 76 patients with morphea: Toward a better understanding of the spectrum of morphea. Arch Dermatol 2012;148:24-8.
Kreuter A, Wischnewski J, Terras S, Altmeyer P, Stücker M, Gambichler T. Coexistence of lichen sclerosus and morphea: A retrospective analysis of 472 patients with localized scleroderma from a German tertiary referral center. J Am Acad Dermatol 2012;67:1157-62.
Hamada T, Wessagowit V, South AP, Asjton GH, Chan I, Oyama N, et al
. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. J Invest Dermatol 2003;120:345-50.
Edmonds EV, Oyama N, Chan I, Francis N, McGrath JA, Bunker CB. Extracellular Matrix Protein 1 (ECM1) Autoantibodies in Male Genital Lichen Sclerosus (MGLSc). Br J Dermatol 2011;165:218-9.
Oyama N, Chan I, Neill SM, Hamada T, South AP, Wessagowit V, et al
. Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet 2003;362:118-23.
Baldo M, Bhogal B, Groves RW, Powell J, Wojnarowska F. Childhood vulval lichen sclerosus: Autoimmunity to the basement membrane zone protein BP180 and its relationship to autoimmunity. Clin Exp Dermatol 2010;35:543-5.
Patsatsi A, Kyriakou A, Mantas A, Vavilis D, Patsialas C, Sotiriadis D. Circulating anti-BP180 NC16a and anti-BP230 autoantibodies in patients with genital lichen sclerosus do not correlate with disease activity and pruritus. Acta Derm Venereol 2014;94(6):711-2.
Kreuter A, Kryvosheyeva Y, Terras S, Moritz R, Möllenhoff K, Altmeyer P, et al
. Association of autoimmune disease with lichen sclerosus in 532 male and female patients. Acta Derm Venereol 2013;93:238-41.
Gambichler T, Belz D, Terras S, Kreuter A. Humoral and cell-mediated autoimmunity in lichen sclerosus. Br J Dermatol 2013;l69:183-4.
Cantwell AR. Histologic observations of pleomorphic, variably acid-fast bacteria in scleroderma, morphoea and lichen sclerosus et atrophicus. Int J Dermatol 1984;23:45-52.
Schempp C, Bocklage H, Lange R, Kölmel HW, Orfanos CE, Gollnick H. Further evidence for Borrelia burgdorferi infection in morphoea and lichen sclerosus et atrophicus confirmed by DNA amplication. J Invest Dermatol 1993;100:717-20.
Eisendle K, Grabner T, Kutzner H, Zelger B. Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol 2008;144:591-8.
Fujiwara H, Fujiwara K, Hashimoto K, Mehregan AH, Schaumburg-Lever G, Lange R, et al
. Detection of Borrelia burgdorferi DNA (B.garinii or B. afzelli) in morphoea and lichen sclerosus et atrophicus tissues of German and Japanese but not of US patients. Arch Dermatol 1997;133:41-4.
British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infec 2011;62:329-38.
Edmonds EV, Mavin S, Francis N, Ho-Yen D, Bunker CB. Borrelia burgdorferi is not associated with genital lichen sclerosus in men. Br J Dermatol 2009;34:88-90.
Prowse DM, Ktori EN, Chandrasekaran D, Prapa A, Baithun S. Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma. Br J Dermatol 2008;158:261-5.
Wang SS, Trunk M, Schiffman M, Herrero R, Sherman ME, Burk RD, et al
. Validation of p16 INK4a
as a marker of oncogenic human papillomavirus infection in cerivical biopsies from a population-based cohort in Costa Rica. Cancer Epidemiol Biomarkers Prev 2004;13:1355-60.
Ishikawa M, Fujil T, Masumoto N, Saito M, Mukai M, Nindl I, et al
. Correlation of p16 INK4a
as an indicator for human papillomavirus infection in cervical adenocarcinomas. Int J Gynecol Pathol 2003;22:378-85.
Masumoto N, Fujii T, Ishikawa M, Saito M, Iwata T, Fukuchi T, et al
. P16 overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix. Hum Pathol 2003;34:778-83.
Edmonds EV, Barton G, Buisson S, Francis N, Gotch F, Game L, et al
. Gene expression profiling in male genital lichen sclerosus (MGLSc). Int J Exp Pathol 2011;92:320-5.
D'Hauwers KW, Depuydt CE, Bogers JJ, Noel JC, Delvenne P, Marbaix E, et al
. Human papillomavirus, lichen sclerosus and penile cancer: A study in Belgium. Vaccine 2012;30:6573-7.
Pilatz A, Altinkilic B, Rusz A, Izykowski N, Traenkenschuh W, Rische J, et al
. Role of human papillomaviruses in persistent and glucocorticoid-resistant juvenile phimosis. J Eur Acad Dermatol Venereol 2013;27:716-21.
Shim TN, de Koning MN, Meys R, Goolamali SI, Francis N, Jameson C, et al
. Prevalence of human papillomavirus in male genital lichen sclerosus, penile carcinoma-in-situ and penile carcinoma: Correlation with p16 INK4a
expression and immune status. Br J Dermatol 2014;171(Suppl 4):76.
Boulinguez S, Bernard P, Lacour JP. Bullous lichen sclerosus with chronic hepatitis C virus infection. Br J Dermatol 1999;137:474-5.
Ena P, Lorrai P, Pintus A, Marras V, Dessy LA. Development of multifocal squamous cell carcinoma in lichen sclerosus et atrophicus of the penis associated to HCV hepatitis. Andrologia 2004;36:38-40.
Shim TN, Bunker CB. Male genital lichen sclerosus (MGLSc) and hepatitis C. Br J Dermato 2012;167:1398-9.
Aidé S, Lattario FR, Almeida G, do Val IC, da Costa Carvalho M. Epstein-Barr virus and human papillomavirus infection in vulvar lichen sclerosus. J Low Genit Tract Dis 2010;14:319-22.
Di Paola GR, Rueda-Leverone NG, Belardi MG. Lichen sclerosus of the vulva recurrent after myocutaneous graft. A case report. J Reprod Med 1982;27:666-8.
Yates VM, King CM, Dave VK. Lichen sclerosus et atrophicus following radiation therapy. Arch Dermatol 1985;121:1044-7.
Milligan A, Graham-Brown RA, Burns DA. Lichen sclerosus et atrophicus following sunburn. Clin Exp Dermatol 1988;13:36-7.
Bjekiæ M, Šipetiæ S, Marinkoviæ J. Risk factors for genital lichen sclerosus in men. Br J Dermatol 2011;164:325-9.
Meffert JJ, Grimwood RE. Lichen sclerosus et atrophicus appearing in an old burn scar. J Am Acad Dermatol 1994;31:671-3.
Abdelbaky AM, Aluru P, Keegan P, Greene DR. Development of male genital lichen sclerosus in penile reconstruction skin grafts after cancer surgery: An unreported complication. BJU Int 2011;109:776-9.
Bunker CB. Development of male genital lichen sclerosus in penile reconstruction skin grafts after cancer surgery: An unreported complication. BJU Int 2012;109:E29-31.
Venn SN, Mundy AR. Urethroplasty for balanitis xerotica bliterans. Br J Urol 1998;81:735-7.
Bracka A. Re: Urethroplasty with abdominal skin grafts for long segment urethral strictures. J Urol 2010;183:1880-4.
Bunker CB. Male genital lichen sclerosus and tacrolimus. Br J Dermatol 2007;157:1040-85.
Bunker CB, Edmonds E, Hawkins D, Francis N, Dinneen M. Re: Pugliese JM, Morey AF, Peterson AC. Lichen sclerosus: Review of the literature and current recommendations for management. J Urol 2007;178:2268-76. J Urol 2009;181:1502-3.
Bunker CB. Re: Kulkarni S, Barbagli G, Kirpekar D, Mirri F, Lazzeri M. Lichen sclerosus of the male genitalia and urethra: Surgical options and results in a multicenter international experience with 215 patients. Eur Urol 2009;55:945-56. Eur Urol 2010;58:e55-6.
Bunker CB. Occlusion, urine and genital lichen sclerosus. Indian J Dermatol Venereol Leprol 2012;78:367-8.
Gupta S, Malhotra AK, Ajith C. Lichen sclerosus: Role of occlusion of the genital skin in the pathogenesis. Indian J Dermatol Venereol Leprol 2010;76:56-8.
Bunker CB, Patel N, Shim TN. Urinary voiding symptomatology (micro-incontinence) in male genital lichen sclerosus. Acta Derm Venereol 2013;93:246-8.
Bunker CB. Comments on the British Association of Dermatologists guidelines for the management of lichen sclerosus. Br J Dermatol 2011;164:894-5.
Shim TN, Andrich DE, Mundy AR, Bunker CB. Lichen sclerosus associated with perineal urethrostomy. Br J Dermatol 2014;170:222-3.
Al-Niaimi F, Lyon C. Peristomal lichen sclerosus: The role of occlusion and urine exposure? Br J Dermatol 2013;168:643-6.
Edmonds EV, Bunker, CB. Nuclear magnetic resonance spectroscopy of urine in male genital lichen sclerosus. Br J Dermatol 2010;163:1355-6.
Baldo M, Ali I, Wojnarowska F. The contribution of drugs to lichen sclerosus. Clin Exp Dermatol 2014;39:234.
Hofer MD, Meeks JJ, Mehdiratta N. Lichen sclerosus in men is associated with elevated body mass index, diabetes mellitus, coronary artery disease and smoking. World J Urol 2014;32:105-8.
Garciá Bravo B, Sánchez P, Rodríguez Pichardo A, Camacho F. Lichen sclerosus et atrophicus. A study of 76 cases and their relation to diabetes. J Am Acad Dermatol 1998;19:482-5.
Barbagli G, Palminteri E, Mirri F, Guazzoni G, Turini D, Lazzari M. Penile carcinoma in patients with genital lichen sclerosus: multicenter survey. J Urol 2006;175:1359-63.
Renaud-Vilmer C, Cavelier-Balloy B, Verola O, Morel P, Servant JM, Desgrandchamps F, et al
. Analysis of alterations adjacent to squamous cell carcinoma of the penis and their relationship with associated carcinoma. J Am Acad Dermatol 2010;62:284-90.
Micali G, Nasca MR, Innocenzi D. Lichen sclerosus of the glans is significantly associated with penile carcinoma. Sex Transm Infect 2001;77:226.
Nasca MR, Innocenzi D, Micali G. Penile cancer among patients with genital lichen sclerosus. J Am Acad Dermatol 1999;41:911-4.
Liatsikos EN, Perimenis P, Dandinis K, Kaladelfou E, Barbalias G. Lichen sclerosus et atrophicus. Findings after complete circumcision. Scand J Urol Nephrol 1997;31:453-6.
Carlson JA, Mu XC, Slominski A, Weismann K, Crowson AN, Malfetano J, et al
. Melanocytic profilerations associated with lichen sclerosus. Arch Dermatol 2002;138:77-87.
El Shabrawi-Caelen L, Soyer HP, Schaeppi H, Cerroni L, Schirren CG, Rudolph C, et al
. Genital lentigiens and melanocytic nevi with superimposed lichen sclerosus: A diagnostic challenge. J Am Acad Dermatol 2004;50:690-4.
Bussen SS. Melanocytic proliferations associated with lichen sclerosus in adolescence. Arch Gynecol Obstet 2009;280:1039-40.
Friedman RJ, Kopg AW, Jones WB. Malignant melanoma in association with lichen sclerosus on the vulva of a 14-year-old. Am J Dermatopathol 1984;6:253-6.
Hassanein AM, Mrstik ME, Hardt NS, Morgan LA, Wilkinson EJ. Malignant melanoma associated with lichen sclerosus in the vulva of a 10-year-old. Pediatr Dermatol 2004;21:473-6.
Rosamilia LL, Schwartz JL, Lowe L, Gruber SB, Quint EH, Johnson TM, et al
. Vulvar melanoma in a 10-year-old girl in association with lichen sclerosus. J Am Acad Dermatol 2006;54:S52-3.
Egan CA, Bradley RR, Logsdon VK, Summers BK, Hunter GR, Vanderhooft SL. Vulvar melanoma in childhood. Arch Dermatol 1997;133:345-8.
Pinto A, Mclaren SH, Poppas DP, Magro CM. Genital melanocytic nevus arising in a background of lichen sclerosus in a 7-year-old female: The diagnostic pitfall with malignant melanoma. A literature review. Am J Dermatopathol 2012;34:838-43.
Turnbull N, Shim TN, Patel N, Mazzon S, Francis N, Bunker CB. Penile primary melanoma in three patients with lichen sclerosus (in draft).
Rao A, Bunker CB. Male genital skin biopsy. Int J STD AIDS 2011;22:418-9.
Mallon E, Ross JS, Hawkins DA, Dinneen M, Francis N, Bunker CB. Biopsy of male genital dermatosis. Genitourin Med 1997;73:421.
Shim TN, Bunker CB. The aetiopathogenesis of male genital lichen sclerosus (MGLSc) Nepal J Dermatol Venereol Leprol 2013;11:1-6.
Neill SM, Lewis FM, Tatnall FM, Cox NH. British Association of Dermatologists' guidelines for the management of lichen sclerosus. Br J Dermatol 2010;163:672-82.
Tausch TJ, Peterson AC. Early aggressive treatment of lichen sclerosus may prevent disease progression. J Urol 2012;187:2101-5.
Tremaine RD, Miller RA. Lichen sclerosus et atrophicus. Int J Dermatol 1989;28:10-6.
Dahlman-Ghozlan K, Hedblad MA, von Krogh G. Penile lichen sclerosus et atrophicus treated with clobetasol dipropionate 0.05% cream: A retrospective clinical and histopathologic study. J Am Acad Dermatol 1999;40:451-7.
Lindhagen T. Topical clobetasol propionate compared with placebo in the treatment of unretractable foreskin. Eur J Surg 1996;162:969-72.
Von Krogh G, Dahlman-Ghozlan K, Syrjänen S. Potential human papillomavirus ractivation following topical corticosteroid therapy of genital lichen sclerosus and erosive lichen planus. J Eur Acad Dermatol Venereol 2002;16:130-3.
What is new?
MGLSc is due to chronic urinary micro incontinence and occlusion. It is treated
with either a short course of ultrapotent topical steroid or circumcision.