RESUMO
Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.
Assuntos
Hidradenite Supurativa , Papulose Atrófica Maligna , Humanos , Secretases da Proteína Precursora do Amiloide/genética , Códon sem Sentido , Hidradenite Supurativa/complicações , Hidradenite Supurativa/genética , Proteínas de Membrana/genética , Mutação , Fatores de Transcrição/genéticaRESUMO
Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease.
Assuntos
Doenças dos Nervos Cranianos/patologia , Papulose Atrófica Maligna/patologia , Doenças do Sistema Nervoso Periférico/patologia , Biópsia , Doenças dos Nervos Cranianos/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Papulose Atrófica Maligna/tratamento farmacológico , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Pele/patologiaRESUMO
Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease.
.Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Doenças dos Nervos Cranianos/patologia , Papulose Atrófica Maligna/patologia , Doenças do Sistema Nervoso Periférico/patologia , Biópsia , Doenças dos Nervos Cranianos/tratamento farmacológico , Evolução Fatal , Papulose Atrófica Maligna/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Pele/patologiaRESUMO
Degos disease, also known as malignant atrophic papulosis, is a rare occlusive vasculopathy of unknown etiology characterized by infarcts in the dermis, gastrointestinal tract, central nervous system, and other organs. It is characterized by papules, which become umbilicated and evolve with a depressed porcelain-white central area, with an erythematous halo with telangiectasias. Histological findings include wedge-shaped dermoepidermal necrosis and blood vessel thrombosis. Approximately 50-60% of patients with systemic symptoms die within 2-3 years, most due to gastrointestinal perforation. We report a typical case, with lethal outcome, in a 45-year-old woman.
Assuntos
Papulose Atrófica Maligna/patologia , Pele/patologia , Biópsia , Evolução Fatal , Feminino , Humanos , Perfuração Intestinal/complicações , Papulose Atrófica Maligna/complicações , Pessoa de Meia-Idade , Trombose Venosa/patologiaRESUMO
Degos disease, also known as malignant atrophic papulosis, is a rare occlusive vasculopathy of unknown etiology characterized by infarcts in the dermis, gastrointestinal tract, central nervous system, and other organs. It is characterized by papules, which become umbilicated and evolve with a depressed porcelain-white central area, with an erythematous halo with telangiectasias. Histological findings include wedge-shaped dermoepidermal necrosis and blood vessel thrombosis. Approximately 50-60% of patients with systemic symptoms die within 2-3 years, most due to gastrointestinal perforation. We report a typical case, with lethal outcome, in a 45-year-old woman.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Pele/patologia , Papulose Atrófica Maligna/patologia , Biópsia , Evolução Fatal , Trombose Venosa/patologia , Papulose Atrófica Maligna/complicações , Perfuração Intestinal/complicaçõesRESUMO
A 30-year-old woman was referred on April 2002 for a plaque that involved the internal aspect of the right leg, an erythema nodosum-like lesion on the lower extremities, and periarthritis on her left ankle. Subsequently, the patient developed anular, atrophic, growing, porcelain-white papules, with a thin rim of erythema and telangiectases over her upper and lower extremities. Clinically and histologically, these lesions were the characteristics of Degos disease. Despite arthritis and myositis that required treatment, low level C3 and C4, positive antinuclear antibodies, and elevated anticardiolipin antibodies only once, in a follow-up of 6 years the patient never developed a specific connective tissue disease or other systemic involvement. In conclusion, because clinical and histological findings of Degos disease might mimic connective tissue diseases, rheumatologists must be aware that this reaction pattern can be seen in a wide clinical spectrum of diseases.
Assuntos
Papulose Atrófica Maligna/patologia , Adulto , Feminino , HumanosRESUMO
Presentamos una paciente de sexo femenino, de 53 años de edad, con manifestaciones cutáneas de enfermedad de Degos, sin compromiso sistémico asociado. Se realiza una revisión actualizada de la bibliografía médica mundial, con una descripción clínica, histopatológica, diagnóstica y terapéutica de la enfermedad.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Papulose Atrófica Maligna/patologia , Papulose Atrófica Maligna/tratamento farmacológico , Dermatopatias/patologia , Extremidades/patologia , Tórax/patologiaAssuntos
Isquemia Encefálica/etiologia , Papulose Atrófica Maligna/complicações , Adulto , Aspirina/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Papulose Atrófica Maligna/patologia , Papulose Atrófica Maligna/terapia , Ticlopidina/uso terapêuticoAssuntos
Adulto , Feminino , Humanos , Isquemia Encefálica/etiologia , Papulose Atrófica Maligna/complicações , Aspirina/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Papulose Atrófica Maligna/patologia , Papulose Atrófica Maligna/terapia , Ticlopidina/uso terapêuticoRESUMO
Degos' disease or malignant atrophic papulosis is a rare vasculopathy characterized by the presence of a typical skin lesion and visceral vascular involvement of small vessels, mainly of the digestive tract or central nervous system. The most interesting fact in this disease is the benign appearance of cutaneous lesion, hiding the occlusion of skin and visceral vessels. The author reports the case of a female patient with systemic lupus erythematosus for eight years. During her follow up, generalized skin papules were observed on the trunk and limbs, sparing her face, hands and feet, compatible with Degos' disease. Additional imaging investigation excluded systemic involvement of the disease. Treatment with acetylsalicylic acid prevented the appearance of new cutaneous manifestations and the patient remains clinically stable on the Outpatient Clinic without complications, until this moment. Malign atrophic papulosis is a rare disease with a poor prognosis. However, its association with systemic lupus erythematosus seems to follow a more benign course, without the typical visceral involvement.