Lichen sclerosus et atrophicus (LSA) is a chronic disorder with a predilection for the anogenital region of middle-aged and elderly women. Cases in childhood are uncommon. About 20% of the patients have extragenital lesions, these sometimes occurring without coexisting genital involvement. Extragenital sites which are affected include the upper part of the trunk, the neck, the upper part of the arms, the flexor surfaces of the wrists, and the forehead. Very rarely, palmar, plantar, and digital skin, the face scalp, mouth and even a surgical or burn scar, and a vaccination site have been involved. Extragenital lesions may rarely follow Blaschko's lines.
LSA may involve the glans, prepuce or external urethral meatus of uncircumcized prepubertal or adolescent males, resulting in phimosis. These lesions, also known in the past as balanitis xerotica obliterans, are not associated with extragenital involvement, although isolated extragenital lesions may be seen in other males, HPV is present in a significant number of penile lesions in children. A case has followed the use of alprostadil as an intracavernous injection for penile dysfunction.
LSA commences as flat, ivory to white papules that coalesce to form plaques of varying size and shape. These develop follicular plugging and progressive atrophy leading to a parchment-like, wrinkled, flat or slightly depressed scar ('cigarette paper atrophy'). Vulval lesions may have secondary lichenification from the pruritus-related scratching or they may coexist with hypertrophic areas, the so-called 'mixed vulval dystrophy'. Infrequently, hemorrhagic bullae form and these may be complicated by the subsequent development of milia. Small nodules have been recorded as an unusual clinical manifestation. Pigmentation due to massive melanin incontinence is another rare finding.
Usually, the disorder is slowly progressive with periods of quiescence. Spontaneous involution may occur, particularly in girls at or about the menarche.
There is controversy concerning the relationship of LSA to morphea. Ackerman believes that LSA is a superficial variant of morphea. Although many authors have reported small numbers of cases of LSA coexisting with or superimposed upon morphea, it is suggested, but not universally accepted, that these patients have morphea with secondary lymphedema and sclerosis of the superficial dermis mimicking LSA both clinically and pathologically. In most, but not all instances, there have been no genital lesions. Some patients with LSA have had coexisting autoimmune diseases. Other rare associations include glucose intolerance or diabetes mellitus, vitiligo and sclerodermatous GVHD.
Extragenital lesions never undergo malignant degeneration, although in the genital region there may, uncommonly, be coexisting or subsequent squamous cell carcinoma. In these circumstances, the tumor usually arises in the hyperplastic areas of what is a mixed vulval dystrophy. Interestingly, there is increased p53 but not Ki67 expression in vulval lesions of lichen sclerosus et atrophicus when compared to non-vulval lesional skin. The p53 changes may be of etiological significance in the development of some squamous cell carcinomas of the vulva arising in LSA. Malignant change has been recorded in 5.8% of penile LSA. Most of these cases had concomitant HPV infection.
Although the etiology of LSA is unknown, attention has been directed at the role of Borrelia burgdorferi, which has been detected by a modified silver stain and immunoperoxydase techniques in lesional skin. It has also been demonstrated by PCR-based techniques and serology. Most of the studies have been from Austria or nearby European countries. Some Borrelia associated cases have been reported from Japan . Attempts at detecting this organism in UK , USA and Australian cases have been unsuccessful. It is possible that this geographical association is related to the presence of the genotypes B. garinii and B. aftehi in Europe , but not in the USA , where B. burgdorferi sensu stricto is the usual species of Borrelia found. This particular strain does not appear to be associated with LSA. B. burgdorferi can also be detected in cases of morphea, Lyme disease and atrophoderma of Pasini and Pierini; this latter condition has been reported in patients with LSA.
In LSA there are numerous epidermotropic and dermal lymphocytes that are CD8, CD57. This profile is usually associated with viral diseases, autoimmune diseases and malignancies. Morphea also exhibits CD57lymphocytes. Clonally expanded populations of T cells have been reported in the infiltrate. This probably represents a response to an antigen, as yet unidentified. Immunological changes appear to occur at all levels of the skin. The histological changes suggest that significant alteration of the extracellular matrix is occurring. This may, in part, be mediated by the decreased epidermal expression of CD44, which can produce increased hyaluronate accumulation in the superficial dermis.
Another finding in LSA is a loss of androgen receptors in lesional skin with disease progression. This may be a secondary effect rather than etiological significance. Certain HLA types (particularly DQ7 but also DQ8 and DQ9) are more frequent in patients with LSA. Familial cases are rare.
Established lesions show hyperkeratosis, follicular plugging, thinning of the epidermis and vacuolar alteration of the basal layer. There is broad zone of sub epidermal edema with homogenization of collagen and poor staining in hematoxylin and eosin preparations. In later lesions, this zone becomes more sclerotic in appearance and shows more eosinophilia.
Basement membrane thickening also occurs. Expression of collagen IV and VII is increased. There is dilatation of thin-walled vessels in the zone and sometimes hemorrhage. Beneath the edema there is a diffuse, perivascular infiltrate of lymphocytes, predominantly of T-cell type in the mid dermis. This infiltrate is sometimes quite sparse in established vulval lesions, and it may contain a few plasma cells and histiocytes. Mast cells and liberated mast cell granules are also present. In vulval lesions there is also more diversity in epidermal changes, with hyperplastic areas in mixed dystrophies. The appendages are usually preserved. Two cases with a lymphohistiocytic and granulomatous phlebitis have been reported.
In the early stages, elastic fibers are pushed downwards by the edematous zone and subsequently destroyed. In contrast, elastic fibers are normal or increased in morphea. Small amounts of acid mucopolysaccharide may be found in this zone. The basement membrane may focally fragment and PAS positive material may be found in the subjacent dermis, partially as homogeneous clumps.
In early lesions, the inflammatory infiltrate is quite heavy and is superficial and band-like, mimicking lichen planus. Basal apoptosis and vacuolar change accompany the infiltrate; that is, there are features of the lichenoid tissue reaction (interface dermatitis). Overlap syndromes with lichen planus have also been suggested. Features favoring a diagnosis of LSA over lichen planus include basilar epidermotropism, basement membrane thickening, epidermal atrophy, loss of papillary dermal elastic fibers paucity of cytoid bodies and a lack of wedge-shaped hypergranulosis. As the edematous zone broadens, the infiltrate is pushed downwards and becomes more dispersed and usually less intense.
In presumptive cases with coexisting morphea, the absence of vacuolar alteration, the lack of a well-defined inflammatory infiltrate beneath the thickened dermis, and the presence of deep dermal changes of morphea are features supporting a diagnosis of morphea without coexisting LSA. Microscopic features of LSA have been recorded, as an incidental finding, in acrochordons and in the skin tag/folds of the perineurn known as infantile pyramidal (perineal) protrusion. Another study of this protrusion showed no histological evidence of LSA.