Hailey- Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in e...Hailey- Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in epidermal cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca2+ pump. We analyzed mutations of the ATP2C1 gene in 2 Japanese patients with HHD. The diagnosis of HHD was made based on the characteristic clinical features and histopathological evidence. All 27 exons and flanking intron boundaries were amplified by polymerase chain reaction and products analyzed by sequencing. As a result, we identified a novel missense mutation (A1087G) in exon 13 of the ATP2C1 gene in a patient. This mutation led the amino acid change from Thr to Ala in the phosphorylation protein domain. Another patient showed no mutation of the gene. These results demonstrate that a spectrum of ATP2C1 gene mutations is present in Japanese HHD patients.展开更多
Background:Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretor...Background:Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretory pathway Ca2+-ATPase (SPCA1, ATP2C1) and the sarco/endoplasmic reticulum Ca2+ATPase type 2 (SERCA2, ATP2A2) genes. Objectives:To investigate calcium regulation in keratinocytes cultured from patients with HHD and DD by measuring intracellular calcium resting levels and the cellular responses to ATP and thapsigargin. Methods The study was carried out using keratinocyte cultures established from four patients with HHD and four with DD. Calcium concentrations were measured with fluorescence ratio imaging using fura-2 loading. Results:Control and HHD keratinocytes displayed approximately the same Ca2+levels in resting phase, while DD keratinocytes showed elevated Ca2+levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca2+] i) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca2+] i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca2+]i after treatment with thapsigargin. Conclusions:The results demonstrate that the defects in SPCA1 and SERCA2 calcium ATPases result in distinct patterns of calcium metabolism. This is also supported by the different clinical features of the diseases.展开更多
Introduction. Only ablative methods lead to long termremission of areas affected by Hailey- Hailey disease: excision/skin graft, cryosurgery, dermabrasion... The method using the CO2 laser is a recent addition in the ...Introduction. Only ablative methods lead to long termremission of areas affected by Hailey- Hailey disease: excision/skin graft, cryosurgery, dermabrasion... The method using the CO2 laser is a recent addition in the management of this dermatitis. We report our experience with this technique in 4 patients. Patients and methods. Carbon dioxide laser vaporization was proposed to 4 patients exhibiting Hailey- Hailey disease resistant to classical treatments. A test under local anesthesia was performed beforehand in all the patients. A 60 year- old man had an immediate reaction and refused to continue treatment. In the other 3 cases, the result of the test at 6 months was considered satisfactory. These patients were treated under general anesthesia in a single area of 50 to70 cm2, and a half- body for comparison. The CO2 laser was used in pulse mode, with successive irradiations, until a homogenous, whitish- yellow aspect with first retraction was obtained. Results. Although the healing delays were long (a mean of 1 month) and required major analgesics over the first few days, the cosmetic results were satisfactory and no abnormal scarring was observed. After a median follow- up of 27 months, no relapse of the disease other than punctiform elements was noted. All the patients wanted treatment of the other remaining affected areas be continued. In 2 patients, CO2 laser vaporization permitted treatment of areas not easily accessible to other ablative methods (around the mouth, the anus and the vulva) with anatomy and normal function spared. Discussion. These results are globally good. Although the time to healing was long, the cosmetic and functional results were always satisfactory, without abnormal scarring. Moreover, in 2 of the patients, CO2 laser was able to treat areas inaccessible to other methods. The reason for the efficacy of ablative methods is debated. Re- epidermization with keratinocytes of appendices and not expressing the molecular defect, and the constitution of dermal cicatricial tissue, are two currently proposed hypotheses.展开更多
Benign familial chronic pemphigus (Hailey-Hailey disease,HHD) is a rare hereditary condition characterized by development of blisters at sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene,...Benign familial chronic pemphigus (Hailey-Hailey disease,HHD) is a rare hereditary condition characterized by development of blisters at sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene, which encodes the human secretory pathway calcium ATPase 1 (hSPCA1), have been identified as possible causative mutations. Studying Hungarian patients with HHD, we found two novel, distinct, heterozygous mutations. In a 65-year-old man with a 41-year history of severe recurrent symptoms, a single nucleotide insertion,1085insA, was detected. In a patient whose symptoms were induced by environmental contact allergens, we found a nonsense mutation, Q506X, in exon 17. Our study further illustrates the diversity of mutational events in the pathogenesis of HHD.展开更多
Hailey-Hailey disease also known as familial benign chronic pemphigus is a rare bullous genodermatosis that affects intertriginous area symmetrically. It presents with flaccid blisters, erosions and maceration resulti...Hailey-Hailey disease also known as familial benign chronic pemphigus is a rare bullous genodermatosis that affects intertriginous area symmetrically. It presents with flaccid blisters, erosions and maceration resulting in increased morbidity, reduced quality of life for affected patients. It is rare in occurrence with an incidence of rate of 1 in 50,000. It is diagnosed with a combination of clinical and histopathological findings. While there is no known cure, its relapsing remitting course can be managed with medication. This case describes an unusual presentation of familial benign chronic pemphigus with a late age of onset of symptoms, atypical distribution and resistant to multiple therapies.展开更多
To the Editor:Hailey-Hailey disease(HHD),first discovered by the brothers Howard and Hugh Hailey,[1]is a genodermatosis at intertriginous sites.Mutation of ATP2C1 on chromosome 3q21-2 coding a calciumdependent ATPase ...To the Editor:Hailey-Hailey disease(HHD),first discovered by the brothers Howard and Hugh Hailey,[1]is a genodermatosis at intertriginous sites.Mutation of ATP2C1 on chromosome 3q21-2 coding a calciumdependent ATPase gives rise to calcium dysfunction within keratinocytes,resulting in acantholysis due to a signal transduction disorder.[2]It has been suggested that this gene mutation combined with irritation such as frequent friction,cold,and ultraviolet exposure leads to the development of HHD.[3]展开更多
文摘Hailey- Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in epidermal cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca2+ pump. We analyzed mutations of the ATP2C1 gene in 2 Japanese patients with HHD. The diagnosis of HHD was made based on the characteristic clinical features and histopathological evidence. All 27 exons and flanking intron boundaries were amplified by polymerase chain reaction and products analyzed by sequencing. As a result, we identified a novel missense mutation (A1087G) in exon 13 of the ATP2C1 gene in a patient. This mutation led the amino acid change from Thr to Ala in the phosphorylation protein domain. Another patient showed no mutation of the gene. These results demonstrate that a spectrum of ATP2C1 gene mutations is present in Japanese HHD patients.
文摘Background:Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretory pathway Ca2+-ATPase (SPCA1, ATP2C1) and the sarco/endoplasmic reticulum Ca2+ATPase type 2 (SERCA2, ATP2A2) genes. Objectives:To investigate calcium regulation in keratinocytes cultured from patients with HHD and DD by measuring intracellular calcium resting levels and the cellular responses to ATP and thapsigargin. Methods The study was carried out using keratinocyte cultures established from four patients with HHD and four with DD. Calcium concentrations were measured with fluorescence ratio imaging using fura-2 loading. Results:Control and HHD keratinocytes displayed approximately the same Ca2+levels in resting phase, while DD keratinocytes showed elevated Ca2+levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca2+] i) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca2+] i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca2+]i after treatment with thapsigargin. Conclusions:The results demonstrate that the defects in SPCA1 and SERCA2 calcium ATPases result in distinct patterns of calcium metabolism. This is also supported by the different clinical features of the diseases.
文摘Introduction. Only ablative methods lead to long termremission of areas affected by Hailey- Hailey disease: excision/skin graft, cryosurgery, dermabrasion... The method using the CO2 laser is a recent addition in the management of this dermatitis. We report our experience with this technique in 4 patients. Patients and methods. Carbon dioxide laser vaporization was proposed to 4 patients exhibiting Hailey- Hailey disease resistant to classical treatments. A test under local anesthesia was performed beforehand in all the patients. A 60 year- old man had an immediate reaction and refused to continue treatment. In the other 3 cases, the result of the test at 6 months was considered satisfactory. These patients were treated under general anesthesia in a single area of 50 to70 cm2, and a half- body for comparison. The CO2 laser was used in pulse mode, with successive irradiations, until a homogenous, whitish- yellow aspect with first retraction was obtained. Results. Although the healing delays were long (a mean of 1 month) and required major analgesics over the first few days, the cosmetic results were satisfactory and no abnormal scarring was observed. After a median follow- up of 27 months, no relapse of the disease other than punctiform elements was noted. All the patients wanted treatment of the other remaining affected areas be continued. In 2 patients, CO2 laser vaporization permitted treatment of areas not easily accessible to other ablative methods (around the mouth, the anus and the vulva) with anatomy and normal function spared. Discussion. These results are globally good. Although the time to healing was long, the cosmetic and functional results were always satisfactory, without abnormal scarring. Moreover, in 2 of the patients, CO2 laser was able to treat areas inaccessible to other methods. The reason for the efficacy of ablative methods is debated. Re- epidermization with keratinocytes of appendices and not expressing the molecular defect, and the constitution of dermal cicatricial tissue, are two currently proposed hypotheses.
文摘Benign familial chronic pemphigus (Hailey-Hailey disease,HHD) is a rare hereditary condition characterized by development of blisters at sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene, which encodes the human secretory pathway calcium ATPase 1 (hSPCA1), have been identified as possible causative mutations. Studying Hungarian patients with HHD, we found two novel, distinct, heterozygous mutations. In a 65-year-old man with a 41-year history of severe recurrent symptoms, a single nucleotide insertion,1085insA, was detected. In a patient whose symptoms were induced by environmental contact allergens, we found a nonsense mutation, Q506X, in exon 17. Our study further illustrates the diversity of mutational events in the pathogenesis of HHD.
文摘Hailey-Hailey disease also known as familial benign chronic pemphigus is a rare bullous genodermatosis that affects intertriginous area symmetrically. It presents with flaccid blisters, erosions and maceration resulting in increased morbidity, reduced quality of life for affected patients. It is rare in occurrence with an incidence of rate of 1 in 50,000. It is diagnosed with a combination of clinical and histopathological findings. While there is no known cure, its relapsing remitting course can be managed with medication. This case describes an unusual presentation of familial benign chronic pemphigus with a late age of onset of symptoms, atypical distribution and resistant to multiple therapies.
基金National Natural Science Foundation of China(81371731)Milstein Medical Asian American Partnership foundation(2017,dermatology)Education Reform Projects of Peking Union Medical College(No.2016zlgc0106).
文摘To the Editor:Hailey-Hailey disease(HHD),first discovered by the brothers Howard and Hugh Hailey,[1]is a genodermatosis at intertriginous sites.Mutation of ATP2C1 on chromosome 3q21-2 coding a calciumdependent ATPase gives rise to calcium dysfunction within keratinocytes,resulting in acantholysis due to a signal transduction disorder.[2]It has been suggested that this gene mutation combined with irritation such as frequent friction,cold,and ultraviolet exposure leads to the development of HHD.[3]
