Pathophysiology, Clinical Manifestations, and Treatment of Lichen Sclerosus: A Systematic Review

Abstract

OBJECTIVETo elucidate current understanding on the pathophysiological mechanism of genital lichen sclerosus (LS), urologic manifestations, and treatment options. MATERIALS AND METHODSThe Medline/PubMed and Embase databases were systematically reviewed for publications pertaining to LS. After applying inclusion and exclusion criteria, references were assessed for relevance to the pathophysiology, presentation, and treatment of LS by title and abstract review by 2 independent reviewers, yielding 186 articles for assessment. RESULTSThe contemporary understanding of the epidemiology and histology of LS is reviewed herein. Additionally, we explore in detail the 3 hypotheses regarding the pathophysiological mechanism contributing to disease presentation: infectious etiology, primary immune dysregulation, and the isotraumatopic response. We summarize the available biological evidence supporting each hypothesis. This discussion provides context for understanding LS morbidity and may spur new avenues of research. For the clinician, we review the clinical presentation of disease, including the risk of progression to squamous cell carcinoma. The current medical and surgical treatment options are also detailed. CONCLUSIONLS remains a potentially insidious disease which may lead to debilitating urinary and sexual dysfunction. Cross disciplinary research should aim for earlier detection, as well as more effective and durable treatment. The exact cause of LS remains unknown. UROLOGY 00: 1−9, 2019.

Penile intraepithelial neoplasia, penile cancer precursors and human papillomavirus prevalence in symptomatic preputium: a cross‐sectional study of 351 circumcised men in Sweden

“…A recently published review of LS establishes that the incidence of LS is thought to be underestimated by as much as 50% and that the diagnosis of LS in acquired phimosis must be based on biopsy [14]. LS can develop into penile cancer in up to 13% of cases [15,16]. In a previous study from our group, we found that LS was a strong risk factor for PeIN, odds ratio (OR) 13.6 (95% CI 5.2–35.5) [17].…”

Skin grafting for penile skin loss

“…Scarring and contracture of this tissue can result in difficulty with urination, sexual function, and exposure of the penis. Malignant transformation is estimated to occur in 2%-8% of cases [1] , thus it is essential to ensure that patients with LS can adequately expose and monitor the penis for malignant changes. While there is no cure for LS, topical steroids may halt progression of the disease and resolve symptoms such as itching, burning, and pain related to inflammation [2] .…”

Lichen sclerosus and hidradenitis suppurativa: Two case reports of a new possible association

“…Despite this strong association, the aetiology of lichen sclerosus remains unknow 1 . It has described a significant positive association with genes regulating HLA class II antigens, which are critical regulators of humoral immunity 1,6 . Perhaps, the development of autoantibodies to an unknown autoantigen may account for the histopathological changes.…”

“…Extracellular matrix protein 1 (ECM1), at the dermal‐epidermis junction, could be implicated as autoantigen, although ECM1 alone may not fully explain lichen sclerosus pathogenesis. Moreover, pro‐inflammatory cytokines are upregulated in lichen sclerosus (IL‐1, IL‐7, IL‐15, IFN‐γ, TNF‐α), suggesting LS is driven by a T helper type 1 (Th1) response 1,6 …”