Recurrent eruption of vesicles and bullae involving predominantly the neck, groin, and axillary regions is characteristic of this disorder. Histologic examination shows numerous acantholytic cells and the suprabasal type of blister formation strikingly resembling that in pemphigus vulgaris ... Recurrent eruption of vesicles and bullae involving predominantly the neck, groin, and axillary regions is characteristic of this disorder. Histologic examination shows numerous acantholytic cells and the suprabasal type of blister formation strikingly resembling that in pemphigus vulgaris malignus. This disorder, which appears to represent a defect in keratinocyte cohesion, was first described by the dermatologist brothers Hailey and Hailey (1939).
Loewenthal (1959) thought that pyogenic bacteria act as a precipitating factor. This possibility is supported by the beneficial effects of antibiotics, use of which has converted this condition into a relatively insignificant disorder. In 4 cases of 1 ... Loewenthal (1959) thought that pyogenic bacteria act as a precipitating factor. This possibility is supported by the beneficial effects of antibiotics, use of which has converted this condition into a relatively insignificant disorder. In 4 cases of 1 family, Burns et al. (1967) and Wilson et al. (1968) found Candida albicans in the lesions and found that the fungus would induce lesions in previously uninvolved skin. Ultraviolet radiation, heat, sweating, and infection of the skin can provoke the abnormality. Malchus et al. (1986) claimed an increased frequency of HLA-B16. Lesions have been reported in a more generalized distribution on the skin (Marsch and Stuttgen, 1978) and even on mucosal surfaces, including those of the vagina, buccal mucosa, and esophagus (Burge, 1992; Wieselthier and Pincus, 1993). In addition, longitudinal white striae of the fingernails may be present. Onset usually is in the third to fourth decade but is delayed until after age 40 in approximately 12% of patients. See also acrokeratosis verruciformis (101900) and Darier-White disease (124200). Burge et al. (1991) demonstrated a widespread subclinical abnormality in keratinocyte adhesion in this disorder. They postulated defective adhesion junctions. In Darier disease, on the other hand, abnormal cell adhesion was demonstrable only in clinically involved skin. The studies were done with suction cups to induce blisters with a quantitative application of negative pressure. Burge (1992) studied 58 patients. The disorder generally presented between the second and fourth decades but delay in diagnosis was common. Asymptomatic longitudinal white bands in the fingernails were found in 71% of 38 patients examined and was considered a helpful physical sign. The nail change had not previously been documented. The disorder is predominantly flexural. Friction and heat or sweating exacerbate the lesions and pain may limit physical activities.
In 21 kindreds with HHD, Hu et al. (2000) identified mutations in the ATP2C1 gene (e.g., 604384.0001-604384.0003), which encodes the human homolog of an ATP-powered pump that sequesters calcium into the Golgi in yeast. Regulation of cytoplasmic calcium ... In 21 kindreds with HHD, Hu et al. (2000) identified mutations in the ATP2C1 gene (e.g., 604384.0001-604384.0003), which encodes the human homolog of an ATP-powered pump that sequesters calcium into the Golgi in yeast. Regulation of cytoplasmic calcium was impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient was attenuated in vivo in HHD patients. Their findings not only provided an understanding of the molecular basis of HHD, but also underscored the importance of calcium control to the functioning of stratified squamous epithelia. In a patient with unilateral segmental exacerbations of HHD, originally reported by Vakilzadeh and Kolde (1985), Poblete-Gutierrez et al. (2004) identified heterozygosity for a splice site mutation in exon 22 of the ATP2C1 gene (604384.0009). Haplotype analysis of the more severely affected segmental skin regions revealed consistent loss of the paternal wildtype allele, confirming the authors' hypothesis that such segmental exacerbations represent a form of mosaicism with hemizygosity for the mutation.