Somatic ATP2A2 mutation in a case of papular acantholytic dyskeratosis: mosaic Darier disease

Papular acantholytic dyskeratosis, also known as acantholytic dermatosis of the vulvocrural (or anogenital) area, is an uncommon eruption reported predominantly in women. This entity manifests with pruritic papules in the groin/anogenital area and less commonly on the chest. The pathobiology of papular acantholytic dyskeratosis is uncertain. A 62‐year‐old woman presented with multiple verrucous‐appearing lesions in the groin and on the chest showing acantholytic dyskeratosis on histopathology. Given histological similarity of these papular acantholytic dyskeratosis lesions to Darier disease due to inherited ATP2A2 mutation, we screened affected and normal tissue and peripheral blood in our patient for mutations in ATP2A2. We found an identical ATP2A2 p.706D>N mutation in multiple independent papular acantholytic dyskeratosis lesions that was not present in uninvolved skin or peripheral blood DNA. These findings establish somatic mosaicism of ATP2A2 mutations as a genetic cause for papular acantholytic dyskeratosis.     

Papular acantholytic dyskeratosis of the genitalia

A 32-year-old man presented with multiple papules on the pubic area for 5 months. There were no subjective symptoms. We could not find any clues for predisposing factors. Pathological examination of the excised papules revealed marked acantholysis and dyskeratosis in the epidermis. The lesions persisted for 5 months after the pathological examination. We consider the present case to be similar to that of Chorzelski et al., papular acantholytic dyskeratosis of the vulva, reported in 1984. We would like to propose this case as papular acantholytic dyskeratosis of the genitalia.     

Rapid response of transient acantholytic dermatosis to selenium sulfide treatment for pityriasis versicolor

The observation of a 51-year-old male patient with transient acantholytic dermatosis (TAD) is briefly reported. The discrete eruption, composed of erythematous escoriated papules and papulovesicles, moderately itching, was located on the back and chest, more permanent during the summer season. The biopsy revealed suprabasal acantholysis and Darier-like elements. Lesions of pityriasis versicolor, confirmed by microscopic examination and fluorescence in Wood's light, were intermingled with TAD in the same patient. A topical treatment with selenium sulfide brought TAD lesions to the disappearance in 1 week. Comments are made in relation with the possibility of Malassezia furfur to induce acantholytic phenomena.     

Cantharidin-induced acantholysis in Darier's disease: does acantholysis initiate dyskeratosis?

We have examined the action of cantharidin on the skin of patients with Darier's disease, and used immunohistological techniques to determine the distribution of desmosomal components, keratin intermediate filaments, and proteases in cantharidin-induced blisters. Cantharidin induced acantho- lysis, but the presence of acantholysis did not trigger the development of the characteristic warty, dyskeratotic papules in patients with Darier's disease. The distribution of desmosomal components. keratins and proteases within the acantholytic keratinocytes in the cantharidin-induced blisters was similar to that previously found in acantholytic cells within lesions of Darier's disease: peripheral staining for extracellular desmosomal components was reduced: some desmosomal components were detected diffusely in the acantholytic cells: basal cell keratin markers were expressed by some suprabasal acantholytic cells, and plasminogen was detected in association with acantholytic cells. Cleavage of desmosomes did not reveal the underlying abnormality in Darier's disease.     

Acantholytic dermatosis localized to genitalia and crural areas of male patients: A report of three cases

A series of 3 cases of acantholytic dermatosis localized to the male genitalia and perineal area with distinct clinical and histological features is presented. These patients did not have a family history of similar disorders and had no evidence of rash elsewhere. Clinically, the eruption was characterized by multiple discrete papules or macerated patches involving the genitalia and the perineum. Histologically, the acantholytic dermatosis had features that resembled both Hailey-Hailey disease and Darier's disease. Similar clinical and histological findings have been reported in females. To the best of our knowledge, this is the first report of these lesions described confined to the genital and perineal areas in male patients. We agree with other authors that this condition may represent a distinct acantholytic eruption in the perineal area that should be distinguished from other generalized blistering acantholytic dyskeratotic disorders dial may also involve the genitalia.     

棘层松解角化不良性表皮痣并发色素性毛表皮痣

报告1例单侧棘层松解角化不良性表皮痣并发色素性毛表皮痣。患者男,40岁。10岁时左侧胸部出现片状多毛区,其间有许多淡红色小丘疹。10年前同侧肢体出现红色疣状丘疹,部分融合。皮损冬轻夏重,伴有轻度瘙痒。皮损组织病理学检查可见表皮乳头瘤样增生,基底层上方棘层松解和裂隙,类似Darier病样改变。     

Papular acantholytic dyskeratosis of the vulva

We describe an 11-year-old girl with a persistent pruritic papular eruption on the vulva. Clinically, the lesions consisted of whitish papules and erosions located on the inner aspect of the labia majora. There was no familial history of skin diseases. Histologically, a biopsy specimen showed difuse hyperkeratosis, parakeratosis, acantholysis throughout the thickness of the epidermis, and the presence of corps ronds. Those findings were consistent with a diagnosis of acantholytic dyskeratosis. At 3 years follow-up, only isolated hyperkeratotic, asymptomatic papules on the same location remained. The occurrence of this focal and sporadic, localized form of acantholytic dyskeratosis seems to be rare in the pediatric population, as we could find no other child with this entity reported in the literature.     

Mosaicism for ATP2A2 mutations causes segmental Darier's disease

Epidermal naevi are localized malformations of the epidermis consisting of verrucoid scaly papules and plaques following Blaschko's lines. Genetic mosaicism has been proposed to underlie the development of linear epidermal naevi. Rarely, epidermal naevi show acantholytic histology similar to Darier's disease, a dominantly inherited skin condition characterized by widespread warty papules. As patients with acantholytic dyskeratotic naevi often give a history of worsening after sun exposure and the lesions are typical of Darier's disease, numerous authors have proposed that these patients have segmental Darier's disease. The postulated relationship has not been proven, however. Recently, we identified ATP2A2, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase isoform 2 as the defective gene in Darier's disease. In this report, we investigated the involvement of ATP2A2 in acantholytic dyskeratotic naevi following Blaschko's lines in two patients. We identified a nonsense mutation (Y894X) in the first patient and a nonconservative glycine to arginine mutation at codon 769 (G769R) in the other patient. These mutations were present in affected skin, and were not detected in unaffected skin or in leukocytes. We conclude that acantholytic dyskeratotic naevi can arise from a somatic mutation in ATP2A2. These individuals are mosaics for the mutation, but the risk of transmission of generalized Darier's disease will depend on whether the germline is affected. Our findings provide further evidence that Blaschko's lines do reflect genetic mosaicism and that the term acantholytic dyskeratotic naevus might be replaced in the future by segmental Darier's disease induced by postzygotic mosaicism. J Invest Dermatol 115:1144-1147 2000     

Papulöse akantholytische Dyskeratose

Papular acantholytic dyskeratosis is a very rare skin disease, which shows a suprabasilar cleft with acantholytic and dyskeratotic cells, simulating the light microscopic picture of Darier disease. In this condition, the lesions are acquired without a genetic basis. We observed a 40-year-old woman with about 200 papules on the lower aspects of her legs; histological examination showed changes similar to Darier disease. Transmission electron microscopy showed a reduced number of desmosomes and perinuclear distribution of tonofilaments. The lesions were successfully treated with cryotherapy with spray technique.     

Papular acantholytic dyskeratosis of the anogenital area with positive direct immunofluorescence results

Acantholytic dyskeratosis is a distinct histological pattern characterized by hyperkeratotic and parakeratotic epidermis with intraepidermal clefts harbouring acantholytic and dyskeratotic keratinocytes. This histopathological pattern is uncommon in dermatoses of the anogenital region. We report a 30-year-old woman who had numerous smooth whitish papules on the labia majora, perineum and perianal region, which coalesced into plaques in some areas. Microscopically, the lesions showed prominent suprabasal and intraspinous acantholysis with dyskeratotic keratinocytes. Direct immunofluorescence examination revealed intercellular Ig G and C(3) within the epidermis. We were unable to find a similar case of papular acantholytic dyskeratosis of the anogenital area with positive direct immunofluorescence findings reported in the literature, thus in this report, the clinicopathological features of a unique case are presented.     

Linear epidermal nevus with acantholytic dyskeratosis in an infant

A 7-month-old boy came to use with flat papules and small erosions on the extensor aspect of his left forearm and a linear arrangement of verrucous papules on the dorsum of his left hand. Histological examination revealed hyperkeratosis, parakeratosis, irregular acanthosis, and marked acantholysis from suprabasal through upper epidermis. This is the first reported case of linear epidermal nevus with acantholytic dyskeratosis in Japan.     

Familiäre dyskeratotische Komedonen Eine seltene Entität

Familial dyskeratotic comedones is a rare autosomal dominant genodermatosis. In childhood or adolescence disseminated keratotic papules develop and gradually increase in number with time. The isolated papules show a central keratotic plug which tends to recur after extraction. Pruritus and occasional inflammation are the only symptoms. The lesions appear on the extremities, and less frequently on the trunk and the face. About half of the patients have a history of acne vulgaris. The histologic picture is highly characteristic and shows a deep invagination of an acantholytic and dyskeratotic epidermis with prominent cornification. Familial dyskeratotic comedones are generally refractory to any therapy. We report on two sisters with familial dyskeratotic comedones successfully treated by CO₂-laser therapy.     

Papular acantholytic dyskeratosis of the vulva

We describe a 63-year-old woman with an asymptomatic papular eruption on the vulva. Clinically, the lesions showed multiple pin-head-sized whitish papules on the labia major. Histologically, the biopsy specimen showed acantholysis throughout the epidermis with the presence of dyskeratotic cells resembling corps ronds and grains, hyperkeratosis and parakeratosis. These clinical and histological findings were consistent with the diagnosis of papular acantholytic dyskeratosis of the vulva which is a rare disorder, first described in 1984.     

暂时性棘层松解性皮病1例

报道1例暂时性棘层松解性皮病，以丘疹为主要临床表现，病理见局限性基底细胞层上裂缝，少量棘层松解细胞。     

Unilateral segmental Darier disease following Blaschko lines: a case report and review of the literature

Darier disease (DD) is an autosomal-dominant skin disorder that is characterized by multiple keratotic papules, loss of epithelial adhesion, and abnormal keratinization. We describe an unusual case of late-onset unilateral segmental DD that follows the lines of Blaschko. Our patient did not exhibit other classic findings of DD. Our case and review of the literature suggest that lesions previously classified as acantholytic dyskeratotic epidermal nevi (ADEN) are actually unilateral segmental presentations of DD.     

Congenital acantholytic dyskeratotic epidermal naevus following Blaschko's lines versus segmental Darier's disease

A Japanese newborn male with an unremarkable family history presented at birth with verrucous papules on the left side of the trunk and limbs, distributed along Blaschko's lines. Histological examination showed mild acantholytic dyskeratosis, consistent with Darier's disease; however, search for mutations of the SERCA gene, performed on DNA extracted from cells from involved and uninvolved skin and peripheral blood proved negative. The absence of detectable SERCA mutations did not allow confirmation of the diagnosis of (segmental) Darier's disease, and a tentative diagnosis of congenital acantholytic dyskeratotic epidermal nevus was considered. The relationship between the two conditions is briefly discussed.     

Zosteriform persistent acantholytic dermatosis and porphyria cutanea tarda

Our case refers to a 77 year-old man with a history of porphyria cutanea tarda (PCT) who presented with pruritic eruption consisting of erythematous papules localized in a zosteriform area on the right part of the trunk which had appeared three years previously. He gave a history of long exposure to the sun. A biopsy showed a spongiotic pattern, dyskeratotic acantholytic cells and corp ronds in the granular layer. Diagnosis of persistent acantholytic dermatosis (Grover's disease) was made. To the best of our knowledge no case of association of PCT and persistent Grover's disease has been previously described in the dermatologic literature.     

生殖器丘疹样棘层松解性皮病一例

报道1例生殖器丘疹样棘层松解性皮病.患者,男,30岁.2年前肛周出现灰白色丘疹,部分融合,伴瘙痒.实验室检查:HPV6阳性,醋酸白试验、梅毒螺旋体明胶凝集试验(TPPA)、HIV均阴性.皮损组织病理示:基底层上方棘层下方多处裂隙,可见棘层松解细胞,中等量淋巴细胞浸润.直接免疫荧光:IgG、IgM、IgA、C3阴性.予以...     

Grover病1例并文献复习

患者男,51岁。躯干及四肢丘疹、水疱及脓疱反复发生30余年,腹股沟角化性丘疹10余天。皮损组织病理检查见表皮局灶性棘层松解,直接免疫荧光阴性。诊断:暂时性棘层松解性皮肤病(Grover病)。并结合本例临床特点进行文献复习。