Necrolytic Erythema Research Articles

Migratory necrolytic erythema as a manifestation of pancreatic neuroendocrine tumor. Clinical-radiological evaluation

ResumenEl glucagonoma es un tumor neuroendocrino de muy baja incidencia, se estima 1 caso cada 20 millones de personas por año. Típicamente, se manifiesta con un síndrome clínico que incluye una dermatosis característica denominada eritema necrolítico migratorio (ENM). Presentamos el caso de un varón de 60 años con ENM como presentación inicial de un tumor pancreático y los hallazgos por imágenes del mismo. Resaltamos la importancia de reconocer las características clínicas del ENM y el rol de los diferentes métodos por imágenes para un diagnóstico precoz y correcto manejo de estos tumores pancreáticos.

Zinc-responsive acral hyperkeratosis as a mimicker of cutaneous tuberculosis

Zinc-responsive acral hyperkeratosis is regarded as a novel entity masquerading numerous skin disorders, such as psoriasis, acral necrolytic erythema, and tuberculosis. Tuberculosis itself is a great imitator and so is its cutaneous form. Herein, we present the case of a female misdiagnosed as a case of tuberculosis verrucosa cutis due to clinical, biochemical, and histopathological features. The patient completed a full course of anti-tubercular therapy without an improvement and showed a dramatic response after a therapeutic trial of oral zinc. Thus, the patient was diagnosed as a case of zinc-responsive acral hyperkeratosis. In any form of acral hyperkeratotic lesions, zinc-responsive acral hyperkeratosis must be considered as a differential diagnosis.

Atypical Presentation of Pancreatic Glucagonoma. New Clinical Presentation before Early Imaging Diagnosis?

Purpose: The aim is to expose the atypical presentation in an early diagnosed glucagonoma case. Method: A 76-year-old man with altered fasting basal glucose levels and a constitutional syndrome of 4 months of evolution, associated with palpitations and pigmented and pruritic skin lesions. Abdominal CT: 14mm hyperdense nodular structure in the pancreatic tail with calcifications. Hormonal study: glucagon> 400 pg / ml. Neuronal specific enolase and CgA positive. Negative tumor markers. Ultrasound-guided FNA: neuroendocrine tumor, glucagonoma. PET-CT: negative for metastasis. Octreoscan: pancreatic injury. Surgical treatment is decided: distal splenopancreatectomy and lymphadenectomy. Results and conclusions: Glucagonoma classically presents with weight loss and the “4 Ds”: diabetes, dermatitis (necrolytic erythema migrans), deep vein thrombosis, and depression. In our case, the presentation is atypical, with little weight loss, skin lesions other than necrolytic migratory erythema and altered fasting blood glucose levels. Are we changing the natural history of these tumors due to their early diagnosis with the increasingly requested imaging? This raises us whether in the future we should suspect them of atypical forms of presentation and whether new therapeutic strategies will be considered as a result of their early diagnosis. Currently, surgical treatment is indicated from the beginning in all sporadic functioning pancreatic neuroendocrine tumors (there are some exceptions in cases of genetic syndromes) and resectable. The surgical indication is for cephalic duodenopancreatectomy or distal splenopancreatectomy depending on the location of the tumor, associated with systematic lymphadenectomy due to its high rates of malignancy and lymph node involvement.

S2619 A Case of Happy Feet—Hepatitis C Necrolytic Acral Erythema in a Hispanic Patient

INTRODUCTION: Necrolytic acral erythema (NAE) was first described in 1996 in Egyptian patients with hepatitis C (HCV) infection. This entity has been strongly associated with HCV as a unique cutaneous marker. In the United States there are 23 cases reported, with a prevalence of 1.7% in 2012. There are rare reports in the literature of this cutaneous finding in the Hispanic population. CASE DESCRIPTION/METHODS: Fifty-four-year old Hispanic man with medical history of hypertension, alcohol abuse and chronic HCV (genotype 2) presented to the outpatient clinic with complaints of bilateral scaly plaques in his feet. The lesions appeared 5 years ago, initially in bilateral toes and then progressed to dorsum of the feet with associated pruritus and pain on light touch. He had tried over the counter topical agents and anti-fungal therapy without improvement. On exam had scleral icterus, with distended abdomen and fluid wave presence. Patient had bilateral hyperpigmented-violaceous scaly and lichenified well-demarcated plaques in dorsal area of feet. Pertinent labs included platelet count of 66th/uL, AST 80IU/L, ALT 83IU/L, Tbili 1.4mg/dL and HCV RNA PCR 2,950,000 copies. Given non-profit outpatient clinic supplies we were unable to obtain punch biopsy. Patient was referred to gastroenterology and was prescribed oral zinc sulfate 150 mg daily for suspected NAE. The patient demonstrated response to the treatment and had resolution of symptoms. DISCUSSION: NAE is a unique cutaneous marker of HCV infection. Pathogenesis remains unclear, HCV RNA peptides and zinc dysregulation may play a role. Most of cases are consistent with distinct acral distribution, HCV positive and zinc deficiency. Symptoms include pruritus in 93% of cases, burning and pain. These lesions present from erythematous-violaceous hyperpigmented plaques to vesicles and flaccid bullae. Differential diagnosis includes other necrolytic erythema such as psoriasis, eczema, pellagra and necrolytic migratory erythema. Skin biopsy shows hyperkeratosis, acanthosis, spongiosis and superficial perivascular lymphocytic infiltrate. Treatment usually involves therapy for underlying HCV infection. However oral zinc supplementation has reported resolution of lesions. From the 23 cases reported in the US, there is only 2 cases in a Hispanic patient. This case represents the third reported Hispanic patient from the US with HCV and necrolytic acral erythema treated successfully with oral zinc. Further cases are needed to define additional treatment options for this rare entity.Figure 1.: Patient's feet showing lesions in dorsal area.Figure 2Figure 3.: Left foot showing scaly violaceous plaques.

Necrolytic Acral Erythema: Current Insights.

Necrolytic acral erythema (NAE) is now considered as a distinct clinical entity. It clinically presents as well demarcated hyperpigmented papules and plaques with thick adherent scales distributed symmetrically over dorsum of feet. It usually develops in patients with Hepatitis C virus (HCV) infection. Cases of NAE have been reported in patients without HCV infection. Hepatic dysfunction resulting in metabolic alterations like hypoalbuminemia, hypoaminoacidemia, hyperglucagonemia and transient zinc deficiency has been proposed as underlying pathogenic mechanism of NAE. Clinically, NAE resembles other necrolytic erythemas like necrolytic migratory erythema (NME), acrodermatitis enteropathica (AE) and pellagra. Better understanding of etiopathogenesis and histopathological features is important to distinguish NAE from other necrolytic erythemas. The disease runs a natural course of exacerbations and remissions. Non-invasive diagnostic tools like dermoscopy can be used in differential diagnosis of NAE. Oral zinc therapy is the most effective treatment of NAE reported in most of the cases irrespective of HCV status or serum zinc levels.

Zinc-responsive acral hyperkeratotic dermatosis-A novel entity or a subset of some well-known dermatosis?

Background:We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.Materials and Methods:Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. A proper history was taken and relevant laboratory investigations were done which included blood count, urine, liver function, renal function, hepatitis-C virus serology and serum zinc levels. Patients were followed up every 2 weeks. Histopathological examinations of the lesional tissue were done at baseline and after 6 weeks of therapy. Patients were given oral zinc daily and no other treatment during the 6 weeks course.Results:All our patients were non-reactive to hepatitis-C. Of the ten patients only one patient (10%) showed low titer of serum zinc, another (10%) showed higher zinc level, while the rest of the patients had normal zinc level. Five of our patients had chronic renal failure, one had Grave's disease and the remaining had no associated systemic illness. Histopathology mostly showed hyperkeratosis, acanthosis, prominent granular layer, spongiosis and dermal infiltrate. After 6 weeks of follow up, all patients showed rapid and remarkable therapeutic response with zinc.Conclusions:We here report a series of patients, discernible because of their uniform clinical presentation of acral hypekeratotic plaques and in showing a noticeable response to zinc. Clinical, histopathological and laboratory investigations were done to rule out diseases of similar morphology including psoriasis, acral necrolytic erythema and lichen simplex chronicus. Authors understand that further studies with greater number cases and more detailed investigations are required to establish exact etio-pathogenesis and nomenclature of this distinct subset of patients.

Diagnosis and treatment of glucagonoma

Glucagonoma is a kind of neuroendocrine tumor of the pancreas,which is rarely seen in clinical practice.Glucagonoma is characterized by necrolytic migratou erythema (NME),diabetes,anemia and body weight loss,and NME is the most characteristic clinical manifestation.The most important laboratory basis of glucagonoma is the levels of fasting plasma glucagon.Various imaging examinations are helpful for the localization of the tumor.Operation is the main method for the treatment of glucagonoma.A patient with glucagonoma was admitted to the Affiliated Hospital of Binzhou Medical College in December 2013,and the experiences in the diagnosis and treatment of glucagonoma were shared based on the data of this patient. Key words: Glucagonoma; Diagnosis ; Treatment

Necrolytic acral erythema

Necrolytic acral erythema is a rare, cutaneous manifestation of hepatitis C virus infection that is characterized by erythematous, violaceous or dusky papules, blisters, and/or erosions in the early stages and by well-demarcated, hyperkeratotic, targetoid plaques with a peripheral rim of macular erythema, secondary lichenification and hyperpigmentation, and overlying fine micaceous or necrotic-appearing scale in the later stages. Because most topical modalities prove ineffective, treatment of the underlying viral infection or therapeutic zinc supplementation are required for clinical improvement.

Necrolytic migratory ulceration

Endocrine tumors of the gastroenteropancreatic system associated with specific skin manifestations are rare. We report a 53-year-old female who presented with migratory annular and arcuate ulcers on her limbs. Histopathology was similar to necrolytic erythema family which includes necrolytic migratory erythema (NME). Though initial CT scans were normal, follow up scans revealed multiple mass lesions in the tail of pancreas. Her skin lesions responded to oral zinc sulphate and monthly injections of octreotide. Prior to planned FNAC from the mass lesion, patient developed altered sensorium and succumbed to the disease. This case report seems to differ from NME clinically, due to unique finding of deep migrating ulcers which heal with scarring. ‘Necrolytic migratory ulceration’ thus appears to be a new paraneoplastic manifestation, secondary to pancreatic malignancy.

Necrolytic Acral Erythema in an Adolescent

In 1996 el Darouti and Abu el Ela described seven Egyptian patients with similar cutaneous lesions and proposed necrolytic acral erythema (NAE) as a distinct entity of the necrolytic erythema family. Since then, NAE has emerged as a cutaneous manifestation of hepatitis C virus infection and taken its place in the literature as a marker for systemic disease. NAE initially presents with burning, pruritic eruptions of circumscribed, erythematous papules with flaccid vesiculation on the acral surfaces universally affecting the dorsum of the feet. The presenting papules of acute NAE evolve over time into confluent, velvety, hyperkeratotic plaques with decreased central erythema but a characteristic dark erythematous rim and adherent scale. Although mostly misdiagnosed as psoriasis or inflammatory dermatitis, NAE can be definitively placed among the necrolytic erythema family as a distinct entity based on clinical and histopathologic characteristics. We report a case of necrolytic acral erythema in a 17-year-old followed by a review of the literature.

Necrolytic acral erythema

Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection and closely related to a group of necrolytic erythemas and metabolic syndromes. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. Based on morphology and histopathologic features, NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. The condition is particularly important for clinicians to diagnose because the majority of the patients present to dermatologists without a known history of HCV infection. Thus, NAE can serve as a cutaneous marker for underlying HCV infection. Resolution of NAE can be achieved by treatment of the underlying HCV infection and the use of oral zinc therapy.

Necrolytic Acral Erythema as a Cutaneous Marker of Hepatitis C: Report of Two Cases and Review

Necrolytic acral erythema (NAE) is a member of the necrolytic erythemas, which include necrolytic migratory erythema (NME), acrodermatitis enteropathica, and various dermopathies secondary to nutritional deficiencies. NAE is distinct from the other necrolytic erythemas by virtue of its consistent association with hepatitisC (HCV) together with the acral distribution of its lesions, in particular, dorsal hands and feet. Although its etiology is unknown, NAE has been reported to respond to zinc replacement, suggesting a causal relationship. Two patients with HCV infection presented with scaly acral plaques and histopathologic features consistent with NAE while also demonstrating atypical palmoplantar accentuation of lesions. Both patients were found to have zinc deficiency, and their lesions responded to zinc supplementation. Awareness of NAE as a unique cutaneous marker for HCV infection is important not only for accurate dermatologic diagnosis but also for appropriate management of associated morbidity and prompt detection of potentially undiagnosed underlying HCV.

Efficacité spectaculaire d’une chimiothérapie par 5 -fluoro-uracile et dacarbazine chez un malade atteint de glucagonome métastatique avec insuffisance cardiaque

Malignant glucagonoma is an exceptional pancreatic endocrine tumour, with frequent dermatologic symptoms, diabetes and degradation of the general health status. Prognosis is unfavourable when liver metastases are present due to the usual inefficiency of chemotherapy. We report here an observation of a patient who was treated for a glucagonoma with multiple liver metastases, migratory necrolytic erythema, dilated cardiomypathy and diabetes that dramatically improved after a dacarbazin-based chemotherapy, allowing subsequent surgical resection of the primary. The patient was still alive and asymptomatic without progressive disease nearly two years after surgery.

Clinical Relevance of Cryglobulinaemia and Extrahepatic Neurocutaneous Manifestations of Chronic Hepatitis C

To examine the prevalence of cryoglobulinaemia in patients with chronic hepatitis C infection and its relation to extrahepatic neuro-cutaneous manifestations. Forty patients (26 males & 14 females), with clinical, laboratory and histologically established chronic hepatitis C infection, with a mean age of 37.5 years, were submitted to clinical examination, dermatological and neurological evaluation. Neuroimaging as well as neurophysiological evaluation, laboratory assessment including liver function tests, serum cryoprecipitate immunoelectrophoresis, and revision of histopathlogical findings were performed. A high prevalence of cryglobulenemia: 62.5% in patients with chronic hepatitis C infection, the presenting symptoms were fatigue (67.5%), arthralgia (32.5%), paresthesia (30%) and pruritus (25%); however, there were no statistically significant difference between cryo +ve versus cryo –ve patients except for pruritis, and face pigmentation. Skin manifestations including face pigmentation (42.5%), leukocytoclastic vasculitis (22.5%), porphyria cutanea tarda (20%), lichen planus (17.5%), acral necrolytic erythema (15%) and vitiligo (15%). Neurological manifestations ; symptomatic neuropathy in 10%, neuropathic changes in 30% and electroencephalographic changes in 22.5%. These cutaneous and neurological manifestations were significantly associated with the presence of cryoglobulinaemia. Our findings support an association between cryoglobuliaemia and extrahepatic neurocutaneous manifestations of hepatitis C infection. The presence of all these manifestations in the appropriate clinical setting should suggest the presence of hepatitis C infection.

Inborn error of amino acid synthesis: Human glutamine synthetase deficiency

Glutamine synthetase (GS) is ubiquitously expressed in human tissues, being involved in ammonia detoxification and interorgan nitrogen flux. Inherited systemic deficiency of glutamine based on a defect of glutamine synthetase was recently described in two newborns with an early fatal course of disease. Glutamine was largely absent in their serum, urine and cerebrospinal fluid. Each of the patients had a homozygous mutation in the glutamine synthetase gene and enzymatic investigations confirmed that these mutations lead to a severely reduced glutamine synthetase activity. From the observation in the first patients with congenital glutamine synthetase deficiency, brain malformation can be expected as one of the leading signs. In addition, other organ systems are probably involved as observed in one of the index patients who suffered from severe enteropathy and necrolytic erythema of the skin. Deficiency of GS has to be added to the list of inherited metabolic disorders as a rare example of a defect in the biosynthesis of an amino acid.

Eritema necrolítico migratorio asociado a glucagonoma

Glucagonoma is a rare pancreatic tumor that is usually associated with a syndrome that includes diabetes, anemia, weight loss and skin lesions in the form of necrolytic migratory erythema. We present the case of a patient with malignant glucagonoma treated with surgery and octreotide, which manifested with skin lesions. The discussion will review the physiopathology, other causes of necrolytic erythema, diagnosis and differential diagnosis and treatment.

Necrolytic Acral Erythema

A 46‐year‐old hepatitis C‐positive African American woman presented with a several month history of worsening, well‐marginated, erythematous, dusky plaques on the dorsum of her feet and ankles. After an initial skin biopsy showed spongiotic dermatitis, she was treated with emollients, high potency topical steroids, and keratolytics, all of which were of no benefit. A punch biopsy from the dorsum of her foot showed acanthosis, individual keratinocyte necrosis, confluent upper epidermal necrosis, and a superficial and deep perivascular lymphocytic infiltrate. Given the patient's positive hepatitis C status and clinicopathological correlation, a diagnosis of necrolytic acral erythema was rendered. Empiric therapy with oral zinc sulfate was initiated despite a normal plasma zinc level, and the skin lesions resolved with post‐inflammatory hyperpigmentation. Necrolytic acral erythema, considered one of the necrolytic erythemas, is a cutaneous manifestation of hepatitis C virus infection. A total of nine cases have been reported in the literature, seven from Egypt and two from the United States. All reported patients have been hepatitis C positive. This case represents the third reported patient from the US with necrolytic acral erythema.

Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity?

Hepatitis C is a major health problem in Egypt. Necrolytic acral erythema (NAE) is a recently described necrolytic erythema that has a distinctive acral distribution and a uniform association with hepatitis C. Some authors believe that NAE is a distinct entity and others consider it as a variant of necrolytic migratory erythema (NME). Five patients with clinical features consistent with NAE were included in this study. The patients were subjected to skin biopsy examination, CT scan of the pancreas and a liver biopsy. Liver function tests, serum glucagon, glucose, amino acids and zinc were measured. All patients were tested for hepatitis C by enzyme-linked immunosorbent assay (ELISA) and by polymerase chain reaction (PCR). Three patients presented with early (acute) lesions and two patients with chronic lesions. The distribution of the lesions was almost exclusively on the dorsae of the feet. Histopathological findings were similar to those of other necrolytic erythemas. Hepatitis C virus was uniformly detected in all patients. Serum glucagon was high in two patients, serum glucose was high in four patients, serum amino acids were low in three cases and serum zinc and albumin were low in two cases. Little or no improvement was reported after oral amino acid supplementation, while the response to oral zinc sulfate was moderate to good. Necrolytic acral erythema is closely associated with hepatitis C infection. Many findings indicate that NAE seems to be a variant of NME rather than a distinct entity. Hence, an alternative proposed term could be acral NME.

Necrolytic acral erythema: response to combination therapy with interferon and ribavirin

Necrolytic acral erythema is a papulosquamous and sometimes vesiculobullous eruption bearing clinical and histologic similarity to other necrolytic erythemas such as necrolytic migratory erythema, pseudoglucagonoma, and nutritional deficiency syndromes. Necrolytic acral erythema is distinguished by its association with hepatitis C infection and its predominantly acral distribution. We describe a pediatric patient with necrolytic acral erythema whose eruption resolved with hyperalimentation and combination interferon and ribavirin therapy, despite the persistence of detectable viral load and continued hepatic and renal insufficiency.

Migratory necrolytic erythema and glucagonoma

Surgery 2003;133:449-50.