Fiona M. Lewis Although rare, a number of genodermatoses may have vulval involvement which requires specific management such as in epidermolysis bullosa. Others may be incidental findings causing no symptoms. However, a knowledge of how genetic problems can present in the skin is important as occasionally the cutaneous features are the first clue to the diagnosis. Genetic disorders involving pigmentation are discussed in Chapter 29. This term describes a variety of genetically determined conditions, characterised by increased fragility of the skin and mucous membranes. Mild trauma can cause blisters, which then heal with scarring. Genetic mutations cause loss of the components of the basement membrane zone. The forms that involve the genital area are the junctional type, in which the splitting occurs in the lamina lucida of the basement membrane, and the dystrophic type, in which the split is below the lamina densa. Extensive erosions and ulceration which heal with scarring can affect the anogenital area (Figure 28.1). These can be present at birth and may be mistaken for traumatic tissue loss during delivery. Fusion of the labia [1] and vagina [2] can occur. One patient presented with lichen simplex on a background of EB simplex [3]. The early onset and frictional lesions at other sites, together with the presence of lesions elsewhere, will usually make the diagnosis of EB straightforward. Urinary complications are common, and obstruction with the potential for chronic renal failure must be monitored [4]. Cutaneous malignancy is increased in these patients, and a vulval squamous cell carcinoma (SCC) has been reported in EB [5]. Figure 28.1 Junctional type epidermolysis bullosa showing extensive erosion after mild trauma. Expert nursing support and education with special attention to the avoidance of the trauma of friction and pressure is required. These patients are managed in expert clinics and need a multidisciplinary approach to their management. Genetic counselling and prenatal diagnosis are available. DEBRA www.debra.org.uk Darier’s disease and Hailey‐Hailey disease (HHD) are the main genetic acantholytic disorders involving the vulva. There are several cases reported of isolated vulval acantholytic lesions without any evidence of family history. This is termed genital papular acantholytic dermatosis (see Chapter 27), but it may be part of a spectrum of similar conditions. Darier’s disease is inherited as an autosomal dominant condition and is caused by mutations in the ATP2A2 gene. These mutations result in abnormal keratinocyte adhesion with loss of desmosomes and breakdown of the desmosome–keratin intermediate filament attachment. There is dyskeratosis with the formation of corps ronds and grains, clefts within the epidermis, and focal areas of acantholysis in the suprabasal layer. The lesions generally develop in childhood or adolescence and may worsen gradually, with fluctuations, but complete remission does not occur. Hyperkeratotic greasy papules arise in the flexures, chest, and scalp, but can involve any site. About 15% of patients have mucosal lesions, which are usually found in the mouth. Vaginal and cervical lesions are recorded, but are rare [6]. The lesions are prone to secondary bacterial and viral infection, and if there is a flare‐up of disease, this is often driven by infection. Lesions are aggravated by heat, oral lithium carbonate, and sometimes menstruation. The differential diagnosis is mainly HHD, which can show considerable overlap with Darier’s disease both clinically and histologically. In Darier’s disease, there are nail changes with splitting, and palmar pits are typical of Darier’s but do not occur in HHD. Neuropsychiatric complications can be associated with Darier’s. One case of a vulval SCC is reported [7]. There are no studies of treatments specifically for the vulva, but therapies used at other sites have been tried. Bland emollients and topical corticosteroids are of limited value. Topical antibacterials may be helpful to reduce infection. Topical retinoic acid may help a little but is irritant. Oral retinoids have been helpful, but their use can be limited due to teratogenicity and side effects. Isotretinoin or alitretinoin are other options due to the shorter half‐life and shorter time after stopping when it is safe to conceive [8]. Ciclosporin is reported to help vulval disease [9]. Radiotherapy, dermabrasion, laser treatment, photodynamic therapy [10], and topical 5‐fluorouracil have been employed, with varying success. There is recent interest in the use of low‐dose naltrexone [11] in the management of both Darier’s and HHD. This is a rare condition, but vulval involvement is common. The inheritance is autosomal dominant with incomplete penetrance. It is caused by mutations in the calcium pump gene ATP2C1, which leads to a defect in keratinocyte adhesion. There is suprabasal splitting and extensive intraepidermal acantholysis, which gives rise to the description of a ‘dilapidated brick wall’ (Figure 28.2). Occasionally, there are a few corps ronds or grains high up in the epidermis. Immunofluorescence is negative. Lesions usually appear in the late teens and affect the genital area as well as flexures elsewhere. Moist, erythematous plaques occur (Figure 28.3
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Genetic Conditions
Epidermolysis bullosa (EB)
Pathophysiology
Clinical features
Differential diagnosis
Complications
Treatment
Resources
Darier’s disease (keratosis follicularis)
Genetics
Pathophysiology
Histological features
Clinical features
Differential diagnosis
Complications
Treatment
Hailey‐Hailey disease (benign familial chronic pemphigus)
Genetics
Histological features
Clinical features
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