Necrolytic Migratory Erythema—A Case Report of Pancreatic Occupying Lesion / 罕见病研究

Glucagonoma is a rare neuroendocrine tumor of α cells of the pancreas. The tumor excessively secretes glucagon and causes glucagonoma syndrome.70%-90% of patients with glucagonoma will develop necrolytic migratory erythema (NME). We reported a patient of glucagonoma syndrome who was presented to the dermatology outpatient clinic with a 2-year-history of recurrent erythema and scaling on the skin migrating throughout the body. A skin biopsy was performed and resulting features matched with NME, whilst imaging examinations suggested a soft tissue density tumor present in the tail of the pancreas with somatostatin receptor expression and laboratory tests found an elevated levels of serum glucagon. After the diagnosis was confirmed, the patient was treated with surgical resection of the glucagonoma and the skin eruptions resolved rapidly in 4 days. Meanwhile, we reviewed relevant literature published in recent years and summarized its clinical characteristics in order to improve its understanding by clinicians, including clinical manifestations, laboratory and imaging examinations, diagnosis and treatments.

Pancreatic glucagonoma with metastasis followed up for 15 years: A case report / 中华内分泌代谢杂志

To explore the clinical characteristics, diagnosis, and management of pancreatic glucagonoma, a retrospective analysis of the clinical data and diagnostic algorithm of a patient with pancreatic glucagonoma was conducted, along with literature review. Pancreatic glucagonoma is a rare neuroendocrine tumor that originates from the pancreatic alpha cells. The main manifestations of glucagonoma syndrome(GS) include necrolytic migratory erythema, diabetes, anemia, and other systemic involvement. Early diagnosis of GS is challenging and crucial. Early identification and recognition of skin lesions contribute to timely diagnosis and treatment of the disease. Surgical resection is an effective treatment modality for glucagonoma.

Dermatosis paraneoplásica asociada a tumor pancreático neuroendócrino / Paraneoplastic dermatosis associated with pancreatic neuroendocrine tumor

RESUMEN 19- Las dermatosis paraneoplásicas son un grupo heterogéneo de manifestaciones cutáneas que tienen fuerte asociación con patología maligna interna. Su patogenia es poco clara y no se conoce su prevalencia exacta. El tratamiento consiste en el abordaje terapéutico de la enfermedad subyacente. La importancia del conocimiento de las mismas radica en la posibilidad de realizar un diagnóstico temprano de una neoplasia. 20- Se presenta el caso clínico de un paciente con dermatosis paraneoplásica asociada a tumor neuroendócrino de páncreas.

ABSTRACT 24- Paraneoplastic dermatoses are an heterogeneous group of cutaneous manifestations that have a strong association with internal malignancy. Their pathogenesis is unclear and prevalence is unknown. Treatment consists of a therapeutic approach to the underlying disease. The importance of recognizingthem lies in the possibility of making an early diagnosis oftheneoplasm. 25- We report theclinical case of a patient with paraneoplastic dermatosis associated with a pancreatic neuroendocrine tumor.

Glucagonoma del páncreas: la piel puede llevarnos al diagnóstico / Pancreatic glucagonoma: observing the skin can lead to diagnosis

Resumen Presentamos el caso de una paciente que tenía un tumor del páncreas -denominado glucagonoma- y cuyo diagnóstico se sospechó por las manifestaciones cutáneas, las cuales nos condujeron realizar una tomografía axial computarizada (TAC). En ella se halló una masa. La paciente se remitió a cirugía y presentó una buena evolución.

Abstract This is a case report of a patient with a pancreatic tumor, known as glucagonoma, whose diagnosis was suspected because of skin manifestations which led to performing a CT scan, finding the mass. She underwent surgery with satisfactory results.

Necrolytic acral erythema in a Chinese patient with hepatitis C and hepatitis B virus coinfection

Abstract: Necrolytic acral erythema is a distinct erythema that has been described as an extrahepatic manifestation of hepatitis C virus infection. Most reported cases have been in Africa, especially Egypt. We report the first case (to the best of our knowledge) of necrolytic acral erythema in a Chinese patient with HCV and HBV coinfection. We aim to increase awareness for recognizing this condition in the Chinese population.

A case of necrolytic acral erythema / 中华皮肤科杂志

A 25-year-old female patient presented with itchy rashes on her feet for 10 years. Skin examination showed dark red plaques with clear boundaries, whose surfaces were covered with grey-brown scales, on the dorsum of toes and adjacent dorsum of the feet, the extensor aspect of the right ankle and the left Achilles tendon. Laboratory tests revealed that serum anti-hepatitis C virus (HCV) antibody was negative and HCV-RNA quantity was normal. Histopathological examination showed epidermal hyperkeratosis with parakeratosis, irregularly thickened spinous layer, scattered dyskeratotic cells and necrotic keratinocytes in the middle and upper spinous layer, focal liquefaction degeneration of basal cells, dilatation of small blood vessels in the superficial and middle dermis, and perivascular infiltration of a small number of lymphocytes. The patient was diagnosed with necrolytic acral erythema without hepatitis C. After 2-month treatment, the skin lesions completely regressed, and hyperpigmentation remained.

A case of necrolytic acral erythema / 中华皮肤科杂志

A 25-year-old female patient presented with itchy rashes on her feet for 10 years.Skin examination showed dark red plaques with clear boundaries,whose surfaces were covered with grey-brown scales,on the dorsum of toes and adjacent dorsum of the feet,the extensor aspect of the right ankle and the left Achilles tendon.Laboratory tests revealed that serum anti-hepatitis C virus (HCV) antibody was negative and HCV-RNA quantity was normal.Histopathological examination showed epidermal hyperkeratosis with parakeratosis,irregularly thickened spinous layer,scattered dyskeratotic cells and necrotic keratinocytes in the middle and upper spinous layer,focal liquefaction degeneration of basal cells,dilatation of small blood vessels in the superficial andmiddle dermis,and perivascular infiltration of a small number of lymphocytes.The patient was diagnosed with necrolytic acral erythema without hepatitis C.After 2-month treatment,the skin lesions completely regressed,and hyperpigmentation remained.

A retrospective study of 14 cases of glucagonoma with literature review / 中华内分泌代谢杂志

Objective To improve the clinical understanding of glucagonoma. Methods A total of 14 cases of glucagonoma were admitted to our hospital, and the clinical features of these cases were retrospectively analyzed. Results (1) The female/ male case ratio was 1 : 1. (2) The median age of onset was 47 years (range 33-61), while the median age at diagnosis was 50 years (range 33-64). (3) The most common initial presentation was necrolytic migratory erythema (7/ 14, 50％). (4) Hyperglycemia was the most common presentation at the time of diagnosis (14/ 14, 100％), followed by necrolytic migratory erythema (13/ 14, 92.9％). (5) The misdiagnosis rate before admission to our hospital was as high as 85.7％ (12/ 14), and the most common misdiagnosis was eczema (7/ 12, 58.3％). (6) The median time from onset of probable symptoms to diagnosis was 4 years. (7) The median plasma glucagon level at diagnosis was 798 pg/ ml (range 200-2853). (8) The median length of the longest tumor diameter of the pancreatic tumors at diagnosis was 4. 0cm ( range 2. 2-8. 0). ( 9) 57. 1％ of primary pancreatic glucagonomas localized in the tail of the pancreas. (10) 57.1％ of patients (8/ 14) had metastases at the time of diagnosis. Conclusions (1)Necrolytic migratory erythema is a relatively sensitive and specific symptom for diagnosis of glucagonoma. (2) The diagnosis for glucagonoma was often delayed, and misdiagnosis was common. ( 3) Most glucagonoma patients had metastases at the time of diagnosis.

Necrolytic acral erythema: a rare skin disease associated with hepatitis C virus infection

Abstract: Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. After blood transfusion and oral zinc supplementation the patient presented an improvement of lesions.

Eritema necrolítico migratorio y glucagonoma pancreático / Necrolytic migratory erythema and pancreatic glucagonoma

El eritema necrolítico migratorio es una dermatosis paraneoplásica infrecuente que puede ser la primera manifestación clínica del glucagonoma, el cual se caracteriza por erupción mucocutánea, intolerancia a la glucosa, hipoaminoacidemia, hiperglucagonemia y glucagonoma pancreático. Se presenta el caso clínico de una mujer de 45 años que presentó pérdida de peso, polidipsia, polifagia, vómito posprandial, caída abundante del cabello y dolor abdominal de dos meses de evolución. Tenía, además, placas eritematosas, descamativas y migratorias en tronco, periné, codos, manos, pies, pliegues submamarios y antecubitales de 20 días de evolución. En la biopsia de piel se observaron células epidérmicas altas con cambio vacuolar notorio, extensa necrosis y delgada capa córnea ortoqueratósica, hallazgos interpretados como eritema necrolítico migratorio. Se sugirió investigar un glucagonoma pancreático. En los exámenes de laboratorio se encontró anemia moderada, hiperglucemia e importante hiperglucagonemia. La ecografía abdominal reveló una masa de 6 x 5 x 5 cm en la cola pancreática, la cual fue resecada. El diagnóstico histopatológico fue de glucagonoma confirmado por inmunohistoquímica. Los síntomas cutáneos desaparecieron a los 10 días de la resección tumoral. Se concluye que los cambios histológicos observados pueden ser claves en la búsqueda de una enfermedad distante de la piel y permiten hacer su diagnóstico. El patrón histológico de vacuolización y necrosis epidérmica subcórnea debe llevar a sospechar la presencia de un glucagonoma pancreático.

Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma.

Glucagonoma syndrome associated with necrolytic migratory erythema / Síndrome do glucagonoma associado a eritema necrolítico migratório

Summary Introduction: glucagonoma is a pancreatic neuroendocrine tumor derived from alpha-cells of the islets of Langerhans. It is marked by tumoral autonomous production of glucagon and characterized, among other symptoms, by necrolytic migratory erythema, an erythematous circinate lesion with areas of necrosis and sloughing. This is a rare disease with worldwide incidence estimated at 1 case per 20 million people. Case report: we report a case of glucagonoma associated necrolytic migratory erythema in a male patient, 56 years, with signs of skin lesions mainly on his legs and groin, hyperglycemia and weight loss. Biopsies of the skin lesions were performed and imaging of the abdomen showed a mass of 10 x 9 cm, at the pancreatic region. The patient was subjected to body-caudal pancreatectomy and splenectomy with autotransplant of the spleen in the greater omentum. The histopathologic report indicated a tumor in the pancreatic alpha cells. Immunohistochemistry showed expression of glucagon and chromogranin A in most tumor cells, consistent with the diagnosis of glucagonoma. The patient presented 3 years of outpatient follow-up with no complications. Conclusion: the necrolytic migratory erythema is important for the clinical recognition of glucagonoma, and its early diagnosis is essential for a successful curative therapy. .

Resumo Introdução: Introdução: o glucagonoma é um tumor neuroendócrino do pâncreas derivado das células alfa das ilhotas de Langerhans. É marcado pela produção tumoral autônoma de glucagon e caracterizado, dentre outros sintomas, por eritema necrolítico migratório (ENM), uma lesão eritematosa circinada com áreas de necrose e descamação. Trata-se de uma doença rara com incidência mundial estimada em 1 caso para cada 20 milhões pessoas. Relato de caso: apresentamos um caso de glucagonoma associado a ENM em um paciente de sexo masculino, 56 anos de idade, com quadro de lesões cutâneas, principalmente em membros inferiores e região inguinal, hiperglicemia e perda ponderal. Biópsias das lesões cutâneas foram realizadas e exames de imagem do abdome evidenciaram uma massa de 10 x 9 cm em região pancreática. O paciente foi submetido à pancreatectomia corpocaudal e esplenectomia total com autoimplante do baço em omento maior. O laudo histopatológico foi de tumor de células alfa pancreáticas. Imuno-histoquímica evidenciou expressão de glucagon e cromogranina A na maioria das células tumorais, compatível com diagnóstico de glucagonoma. O paciente apresentou seguimento de 3 anos em ambulatório sem intercorrências clínicas. Conclusão: o ENM é importante para o reconhecimento clínico do glucagonoma, sendo seu diagnóstico precoce fundamental para uma terapia curativa de sucesso. .

Eritema necrolítico migratorio: a propósito de un caso / Necrolytic migratory erythema: a case report

Presentamos el caso de una paciente de 62 años con un cuadro de tres años de evolución, caracterizado por placas y pápulas eritematosas arciformes que comenzaron en cara, extendiéndose luego al resto del cuerpo, asociado a baja de peso y depresión. Después de un completo estudio y dos biopsias de piel se diagnóstica eritema necrolítico migratorio (ENM). El ENM junto con estomatitis/glositis, baja de peso, diarrea, diabetes y anemia forman el síndrome paraneoplásico asociado al tumor de células a pancreáticas, llamado síndrome del glucagonoma, El ENM corresponde a lesiones maculopapulares, coalescentes, de borde serpiginoso, acompañadas de una bula central que se erosiona y forma costras. La biopsia cutánea muestra hiperplasia psoriasiforme y espongiótica, paraqueratosis y separación de las capas superficiales de la epidermis. La resección del tumor conduce a la resolución del ENM. Presentamos este caso y revisión del tema por la baja frecuencia de esta enfermedad y para reforzar lo importante de su sospecha temprana.

We report the case of o 62 year old woman with a 3 year history of erythematous arciform plaques and papules that began in the face and spread to the rest of the body. These lesions were associated with depression and weight loss. After a comprehensive study and two skin biopsies, necrolytic migratory erythema (NME) was diagnosed together with glossitis/stomatitis, weight loss, diarrhea, diabetes and anemia, NME is part of the paraneoplastic syndrome associated with a cell pancreatic tumor, known as glucagonoma syndrome NME lesions are characterized by a coalescent maculopapular rash with a serpiginous edge and a central bulla that erodes and become crusted. Histological studies show a psoriasiform and spongiotic hyperplasia, porakeratosis, and detachment of the superficial layers of the epidermis. ENM usually resolves after tumor resection. We present this case and a review of the literature because of the low frequency of this disease and to reinforce the importance of its early suspicion.

Necrose epidérmica metabólica em cães / Metabolic epidermal necrosis in dogs

A necrose epidérmica metabólica é uma rara enfermidade endócrino-metabólica, com importantes manifestações cutâneas, possuindo paralelo clinicopatológico com o eritema necrolítico migratório em humanos. O presente estudo tem por objetivo relatar três casos clínicos de NEM em cães acometidos por dermatite eritematosa, crostosa e ulcerativa associada à hepatopatia. O diagnóstico definitivo foi alcançado a partir do exame dermatopatológico. O prognóstico é desfavorável e os três animais morreram, apesar do tratamento.

Metabolic epidermal necrosis is a rare endocrine metabolic disease, characterized by dermatological signs which has clinical and pathological similarity with necrolytic migratory erythema in humans. The present report describes three cases of MEN in dogs affected with erythematous ulcerative crusting dermatitis associated with hepatopathy. The diagnosis was based on cutaneous histopathology. The prognosis is poor and the three dogs died despite the treatment.

A Case of Glucagonoma Syndrome Diagnosed as Necrolytic Migratory Erythema / 대한피부과학회지

Necrolytic migratory erythema (NME) is a typical cutaneous manifestation of glucagonoma syndrome. The entire syndrome consists of NME, glucose intolerance, weight loss, anemia, glossitis, diarrhea, and increased glucagon levels. We herein report a patient with glucagonoma syndrome who was diagnosed as having NME. A 48-year-old male presented with a 2-month history of painful erythematous, desquamative, erosive papules and plaques on both lower extremities. Histological examination revealed an intraepidermal cleft, the presence of vacuolated, pale epidermal cells, and necrosis in the upper epidermis. His glucagon level was 2650 pg/ml, with the upper limit of a normal range being 250 pg/ml. The patient was treated with octreotide, and showed an improvement of the skin eruption with normalization of the glucagon level within 4 weeks.

A Case of pseudoglucagonoma Syndrome Treated with Medium-chain Triglyceride / 대한피부과학회지

Necrolytic migratory erythema is a rare, distinctive, necrotizing cutaneous eruption usually associated with glucagonoma, an alpha-cell tumor of the pancreas. Other clinical features include ane- mia, diabetes mellitus and weight loss. However, it also occurrs without the pancreatic glucagonoma. So this rare condition is called pseudoglucagonoma syndrome, and has been described in association with chronic hepatic diseases, malabsorption with villous atrophy, chronic pancreatitis, celiac sprue, hypoproteinemia and odontogenic infection. We report a case of pseudoglucagonoma syndrome induced by malnutrition without glucagonoma. A 28-year-old Korean female was referred to our department complaining of multiple erythematous, desquamative, crusted and erosive patches on the extremities, and diffuse scalp alopecia for 5 years. She also had perianal erosion, angular cheilitis without glossitis, amenorrhea, axillary and pubic hair loss, and weight loss. Six years previously she had had Whipples operation for a pancreatic solid and papillary neoplasm. The laboratory data showed hypoalbuminemia, essential fatty acid deficiency, diabetes mellitus and slightly high levels of zinc and glucagon. A skin biopsy showed irregular acanthosis, epidermal edema and pallor, dyskeratosis, areas of superficial epidermal necrosis and vascular dilatation of the papillary dermis. The patient improved dramatically after intravenous hyperalimentation and oral intake of mediurn chain triglyceride. For 2.5 years she has taken medium-chain triglycerides without any other treatment, and no side effects on recurrence has been observed.

A Case of Necrolytic Migratory erythema Induced by a Pancreatic Insufficiency / 대한피부과학회지

Necrolytic migratory erythema is a cutaneous reaction pattern with specific histopathologic features that is typically associated with a functioning pancreatic islet cell neoplasm such as a glucagonoma. However, cases without. glucagonoma have also been reported, such as, liver cirrhosis, chronic pancreatitis, celiac sprue etc. Other clinical features include anemia, glossitis and weight loss. We report a case of neccrolytic migratory erythema induced by a pancreatic insufficiency without glucagonoma. A 43-year-old male was seen at our department because of rnultiple erythematous, desquamative and erosive patches on the whole body for 1 month. He also had weight loss(25Kg) and stomatitis. Seven years previously he had a Whipple's procedure for a pancreatic head rupture. The laboratory data showed a low protein and zinc level, and high glucagon level. Histopathologic findings of the case showed epidermal edema and pallor, and superficial epiderrnal necrosis. The patient improved progressively after intravenous infusion of amino acids with a pancreatic enzyme supplementation.