Category: 8. Health

SYDNEY – An Australian man has died from an “extremely rare” rabies-like infection transmitted by a bat bite, health officials said on July 3.

The man in his 50s was bitten by a bat carrying Australian bat lyssavirus several months ago, the health service in New South Wales said.

“We express our sincere condolences to the man’s family and friends for their tragic loss,” NSW Health said in a statement.

“While it is extremely rare to see a case of Australian bat lyssavirus, there is no effective treatment for it.”

The man from northern New South Wales, who has not been identified, was this week listed as being in a “critical condition” in hospital.

Officials said he was treated following the bite and they were investigating to see whether other exposures or factors played a role in his illness.

The virus – a close relative to rabies, which does not exist in Australia – is transmitted when bat saliva enters the human body through a bite or scratch.

First symptoms can take days or years to appear.

Early signs of the disease are flu-like – a headache, fever and fatigue, the health service said.

The victim’s condition rapidly deteriorates, leading to paralysis, delirium, convulsions and death.

There were only three previous cases of human infection by Australian bat lyssavirus since it was first identified in 1996 – all of them fatal.

People should avoid touching or handling bats, as any bat in Australia could carry lyssavirus, the New South Wales health service said.

Only wildlife handlers who are trained, protected, and vaccinated should interact with the flying mammals, it warned.

“If you or someone you know is bitten or scratched by a bat, you need to wash the wound thoroughly for 15 minutes right away with soap and water and apply an antiseptic with anti-virus action,” it said.

“Patients then require treatment with rabies immunoglobulin and rabies vaccine.”

The virus has been found in species of flying foxes and insect-eating microbats, NSW Health said.

The species of bat involved in the latest fatality has not been identified.

“Australian bat lyssavirus is very closely related to rabies and will cause death in susceptible people if they become infected and are not treated quickly,” said Professor James Gilkerson, infectious diseases expert at the University of Melbourne.

Australian bat lyssavirus was first identified in May 1996 by scientists at the national science agency Csiro, who examined brain tissue from a flying fox that had been showing “nervous signs” in New South Wales.

Later that year, a bat handler in Queensland became ill.

“The initial numbness and weakness suffered in her arm progressed to coma and death,” the science agency said in an online document on the virus.

“Two further cases in Queensland – a woman in 1998 and an eight year old boy in 2013 – resulted in death after being bitten or scratched by a bat,” it said.

There are subtle differences between the lysssavirus in flying foxes and insectivorous bats, the science agency has found.

Infected bats can transmit the virus to people, other bats and other mammals. AFP

AustraliaInfectious diseasesAnimals

Prenatal exposure to ambient fine particulate matter and climatic factors, such as temperature and rainfall, are associated with adverse birth outcomes in India, according to a study published July 2nd, 2025, in the open-access journal PLOS Global Public Health by Mary Abed Al Ahad from the University of St Andrews, U.K.

Ambient air pollution poses a global threat to human health, with a disproportionate burden of its detrimental effects falling on those residing in low and middle-income countries. Referred to as the silent killer, ambient air pollution is among the top five risk factors for mortality in both males and females. With a diameter of less than 2.5 microns, ambient fine particulate matter 2.5 (PM2.5), which primarily originates from the burning of fossil fuels and biomass, is considered the most harmful air pollutant. In the 2023 World Air Quality Report, India was ranked as the third most polluted country out of 134 nations based on its average yearly PM2.5 levels.

Ambient air pollution has been associated with a range of pediatric morbidities, including adverse birth outcomes, asthma, cancer, and an increased risk of chronic diseases. Most studies investigating the association between ambient air pollution and adverse birth outcomes have primarily been conducted in high-income countries. Despite the alarming rise in air pollution levels in India, there has been a paucity of research exploring its impact on adverse birth outcomes.

To address this knowledge gap, the researchers investigated the impact of ambient air pollution on adverse birth outcomes at the national level, focusing on low birth weight and preterm birth, and used different geospatial models to highlight vulnerable areas. The analysis provided evidence of the association between in-utero exposure to PM2.5 and adverse birth outcomes by leveraging satellite data and large-scale survey data. The individual-level analysis revealed that an increase in ambient PM2.5 is associated with a greater likelihood of low birth weight and preterm birth. Climatic factors such as rainfall and temperature were also linked to adverse birth outcomes. Children residing in the Northern districts of India appeared to be more susceptible to the adverse effects of ambient air pollution.

According to the authors, the geostatistical analysis underscores the need for targeted interventions, particularly in Northern districts. In addition, the National Clean Air Program should be intensified, with stricter emission standards and enhanced air quality monitoring. Climate adaptation strategies, such as developing heat action plans and improving water management, should be incorporated into public health planning to mitigate the effects of extreme temperatures and irregular rainfall. Public health initiatives should be implemented to raise awareness of the risks of air pollution and climate change, particularly among pregnant women. 

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A team of researchers from the San Raffaele-Telethon Institute for Gene Therapy (SR-TIGET, Milan), led by Nadia Coltella and Luigi Naldini, has unveiled a powerful strategy to rejuvenate the effectiveness of chimeric antigen receptor (CAR) T cell therapy against glioblastoma, one of the most lethal and treatment-resistant brain tumors. The findings, published in Science Translational Medicine, highlight how gene therapy targeting immune stimulating cytokines to the tumor microenvironment (TME) and enabling their private cross-talk with CAR-T cells not only restores CAR-T killer activity but also boost a broader immune response that inhibits tumor growth and extends host survival in a preclinical glioblastoma models.

The study builds on the prior development by the Naldini’s laboratory of a gene therapy strategy that exploit genetic engineering of hematopoietic progenitors to generate a progeny of monocyte/macrophages that selectively release their immune stimulating payload upon infiltrating a tumor. This strategy has been taken to its first-in-human clinical testing as stand-alone treatment of glioblastoma by the biotech company Genenta Science, a spin-off from the San Raffaele Institute now listed on the NASDAQ.

“Solid tumors like glioblastoma have been notoriously difficult for CAR-T cells to penetrate and control,” explains Dr. Rossari, first author of the work, “By reprogramming a population of tumor-infiltrating macrophages to deliver cytokines directly into the tumor, we’ve morphed the immunosuppressive TME into one supportive of immune cells, thus allowing CAR T cells to better persist, become activated and attack tumor cells.”

CAR-T cells have shown transformative results in blood cancers but have struggled in solid tumors due to the hostile, immunosuppressive TME. The team’s strategy leads to selective release of two cytokines within the TME: interferon-α (IFN-α), a pleiotropic immune stimulator that counteracts local immune suppressive cues and enforces antigen presentation and immune effectors’ activity, and an engineered mutant of interleukin-2 that can only activate a cognate mutant receptor co-introduced with the CAR into T cells, thus boosting the proliferation specifically of the administered effector engaged in fighting the tumor.

“The private ‘cross-talk’ between genetically engineered macrophages and CAR T cells established in the TME ensures that the immune stimulants act only where needed, sparing the rest of the body from systemic toxicity, and specifically on the relevant target cells involved in the tumor attack, again preventing collateral damage and aberrant effects,” says Dr. Alvisi, co-first author of the study.

In a mouse model of glioblastoma that mimics the pathology and immunological barriers seen in human patients, the targeted cytokines rescued the activity of CAR-T cells that, given alone, were ineffective – as mostly seen in clinical trials. In turn, the rescued CAR T cells now synergized with cytokine delivery, significantly enhancing their effect on delaying tumor growth and extending mouse survival. Strikingly, even tumors with only a fraction of cells expressing the CAR-targeted antigen B7-H3 were effectively controlled, indicating engagement of endogenous T cells on top of the CAR-T to fight the tumor.

“We observed not only reactivation of the CAR-T cells but also the recruitment of the host’s own T cells against a wider range of tumor antigens,” says Dr. Nadia Coltella, senior co-corresponding author. “This phenomenon, known as antigenic spreading, was mostly dependent on IFN-α activity in the TME and is a key feature for creating effective immunity as it may overcome immune evasion by tumors targeted only through a single antigen by the CAR-T cells.”

“This work represents another important step forward in our decade-long commitment to develop a novel gene and cell therapy strategy effective against tumors, as we have been able to do for several genetic diseases along the life of our institute” adds Luigi Naldini, Director of SR-TIGET and Professor at Università Vita-Salute San Raffaele. “The tumor-targeted IFN-α delivery strategy is already being evaluated as stand-alone treatment in a first-in-human phase 1/2a trial on the most aggressive type of glioblastoma (Temferon trial) led by the biotech company Genenta Science. The study has shown feasibility, safety, biological activity in reprogramming the TME and early but promising indication of therapeutic benefit, albeit limited by the small number of treated patients and the design of a phase 1 study. A combination of Temferon with CAR-T cells administration, as prompted by our new study, could in future further enhance the benefit of the treatment and broaden its efficacy to a larger fraction of patients.”

This study was supported also by the Italian Association for Cancer Research (AIRC), the Louis-Jeantet Foundation through the Jeantet-Collen Prize for Translational Medicine to Luigi Naldini, and a research contract from Genenta Sciences.

Your mouth is a magician. Bite the inside of your cheek, and the wound may vanish without a trace in a couple of days. A preclinical study co-led by Cedars-Sinai, Stanford Medicine and the University of California, San Francisco (UCSF), has discovered one secret of this disappearing act. The findings, if confirmed in humans, could one day lead to treatments that enable rapid, scarless recovery from skin wounds on other parts of the body.

The study was published in the peer-reviewed journal Science Translational Medicine.

Our research began with two questions: Why does your mouth heal so much better than your skin? And if we figure that out, can we use that information therapeutically?”

Ophir Klein MD, PhD, executive vice dean of Children’s Health at Cedars-Sinai, executive director of Cedars-Sinai Guerin Children’s, the David and Meredith Kaplan Distinguished Chair in Children’s Health and co-corresponding author of the study

The need for therapies is clear. Wounds to the lining of the mouth typically disappear in one to three days. But skin wounds may take nearly three times as long to heal and can leave unsightly scars.

“Unfortunately, current treatments do not adequately resolve or prevent scarring because we do not fully understand the mechanism,” Klein said. “Our research helps fill in that knowledge gap.”

In the study, investigators analyzed tissue samples from the lining of the mouth, known as the oral mucosa, and the facial skin of laboratory mice. In the oral mucosa, they found a signaling pathway between cells, involving a protein called GAS6 and an enzyme called AXL, which blocks a different cellular pathway, known as FAK, that promotes scarring.

When the investigators inhibited the AXL enzyme in the laboratory mice, the oral mucosa wounds’ healing worsened, making them more like skin wounds. When AXL was stimulated in the skin wounds, they healed much like oral mucosa wounds, regenerating tissue more efficiently.

“This data shows that the GAS6-AXL pathway is potentially important for scarless healing in the mouth and that manipulating it may help reduce skin scars as well,” Klein said.

The next steps are to further determine how these preclinical findings apply to humans and to develop therapies to improve healing of skin wounds, according to Michael Longaker, MD, the Dean P. and Louise Mitchell Professor in the School of Medicine at Stanford University, and the study’s co-corresponding author.

“Further clinical studies should be performed to assess the nature of the relationship between AXL and scarring in humans,” Longaker said.

Microplastics are particles ranging from 1 micrometer to 5 millimeters in diameter, and nanoplastics, which are even smaller, are found in virtually every environment on Earth, from mountain peaks to ocean depths, and from the smallest animals in the food chain to human brain cells.

These particles can originate from the breakdown of larger plastic items or be intentionally manufactured for use in products, such as cosmetics, synthetic fabrics, and pharmaceuticals. Recent studies suggest that the human brain may contain up to a teaspoon of microplastics and nanoplastics, with the tiniest fragments primarily composed of polyethylene, the same material commonly used in plastic bags and food packaging.

These particles have been detected in areas such as the walls of blood vessels in the brain and within immune cells. However, it remains unclear whether microplastics contribute to the progression of neurological diseases or whether these conditions render the brain more susceptible to particle infiltration. In animal studies involving fish and rodents, prolonged exposure to nanoplastics has been linked to memory impairment, brain inflammation, and alterations in synaptic protein levels.

Beyond the brain, microplastics have been found in human feces, arterial plaques, and even the placenta. A study published in The New England Journal of Medicine linked the presence of microplastics in the arteries to a heightened risk for heart attack, stroke, and overall mortality.

Therapeutic Apheresis

According to a preliminary study published in Brain Medicine by researchers at Technische Universität Dresden in Dresden, Germany, therapeutic apheresis, a medical procedure that filters tiny particles from the blood, may help remove microplastics from the human body. The technique can capture particles as small as 200 nanometers, which is approximately 5000 times smaller than a millimeter.

In this study, the researchers evaluated the procedure in patients with myalgic encephalomyelitis, also known as chronic fatigue syndrome. They analyzed the waste fluid discarded during apheresis using a specialized infrared spectroscopy technique.

The analysis detected substances that matched the chemical signatures of polyamide and polyurethane, two common types of industrial plastics. This suggests that microplastics may have been successfully removed from the blood of patients during the procedure.

Notably, this study did not measure the total amount of microplastics removed or compare their levels in patients before and after apheresis. What has been demonstrated so far is the presence of microplastics in the waste material discarded by the device — an observation that suggests, but does not yet confirm, the effective removal of these substances from the human body.

Researchers have cautioned that the detected materials may reflect chemical structures common to proteins, meaning that further analysis is required to verify the exact nature of the removed particles. Nonetheless, the findings offer hope to researchers seeking to address the growing accumulation of microplastics in the human body.

The authors recommended conducting studies with larger groups and quantitative analyses comparing the levels of microplastics in the blood before and after the procedures. The authors concluded that “such analyses will help determine particle removal from blood and tissues and assess correlations with symptom improvement in conditions like myalgia encephalomyelitis/chronic fatigue syndrome.”

Alternative Approaches

Currently, evidence that microplastics are effectively removed from the human body after ingestion is limited.

A 2011 study examined bisphenol A (BPA) levels in blood, sweat, and urine samples from 20 individuals. In 16 cases, BPA appeared only in sweat, suggesting that induced perspiration may help eliminate certain compounds from the body. However, more studies are needed to assess its long-term safety and efficacy.

“That is why we focus on reducing exposure to microplastics in the first place,” said Nicholas Fabiano, MD, a psychiatry resident at the University of Ottawa, Ottawa, Ontario, Canada, and co-author of a related article in Brain Medicine.

The challenge of this research began with tracking the effects of microplastic particles. “From a clinical perspective, it is very difficult to establish a direct link between exposure to microplastics and adverse health outcomes,” said Fabiano.

To address this, he advocated the creation of new tools to measure dietary risks, such as a dietary microplastic index. “We propose the development of a Dietary Microplastic Index that could be integrated with existing dietary risk assessment tools to estimate microplastic exposure based on the types of food consumed,” he said.

This story was translated from Medscape’s Portuguese edition. 

As brain tumors grow, they must do one of two things: push against the brain or use finger-like extensions to invade and destroy surrounding tissue.

Previous research found tumors that push – or put mechanical force on the brain – cause more neurological dysfunction than tumors that destroy tissue. But what else can these different tactics of tumor growth tell us?

Now, the same team of researchers from the University of Notre Dame, Harvard Medical School/Massachusetts General Hospital, and Boston University has developed a technique for measuring a brain tumor’s mechanical force and a new model to estimate how much brain tissue a patient has lost. Published in Clinical Cancer Research, the study explains how these measurements may help inform patient care and be adopted into surgeons’ daily workflow.

During brain tumor removal surgery, neurosurgeons take a slice of the tumor, put it on a slide and send it to a pathologist in real-time to confirm what type of tumor it is. Tumors that originally arise in the brain, like glioblastoma, are prescribed different treatments than tumors that metastasize to the brain from other organs like lung or breast, so these differences inform post-surgical care. By adding a two-minute step to a surgeon’s procedure, we were able to distinguish between a glioblastoma tumor versus a metastatic tumor based on mechanical force alone.” 

Meenal Datta, assistant professor of aerospace and mechanical engineering at Notre Dame and co-lead author of the study

Datta and collaborators collected data from 30 patients’ preoperative MRIs and their craniotomies, which include exposing the brain and using Brainlab neuronavigation technology. This technology provides surgeons with real-time, 3D visualization during brain surgeries and is considered commonly available for neurological procedures. Neurosurgeons can use this technique to measure the bulge caused by brain swelling from the tumor’s mechanical forces before the tumor is resected.

Then this patient data was used to determine whether brain tissue was displaced by a tumor’s mechanical force or replaced by a tumor. The researchers found that when there is more mechanical force on the brain (displacement), the swelling will be more substantial. But when a tumor invades and destroys surrounding tissue (replacement), the swelling will be less significant.

The researchers created computational models based on a point system of measurements and biomechanical modeling that can be employed by doctors to measure a patient’s brain bulge, to determine the mechanical force that was being exerted by the tumor, and to determine the amount of brain tissue lost in each patient.

Funded by the National Institutes of Health, National Science Foundation and various cancer research foundations, this study is among the first to show how mechanics can distinguish between tumor types.

“Knowing the mechanical force of a tumor can be useful to a clinician because it could inform patient strategies to alleviate symptoms. Sometimes patients receive steroids to reduce brain swelling, or antipsychotic agents to counter neurological effects of tumors,” said Datta, an affiliate of Notre Dame’s Harper Cancer Research Institute. Datta recently showed that even affordable and widely used blood pressure medications can counter these effects. “We’re hoping this measurement becomes even more relevant and that it can help predict outcomes of chemotherapy and immunotherapy.”

To get a better idea of what else mechanical force could indicate, the research team used animal modeling of three different brain tumors: breast cancer metastasis to the brain, glioblastoma and childhood ependymoma.

In the breast cancer metastasis tumor, researchers used a form of chemotherapy that is known to work in reducing metastasis brain tumor size. While waiting for the tumor to respond to the chemotherapy, the team found that a reduction in mechanical force changed before the tumor size was shown to change in imaging.

“In this model, we showed that mechanical force is a more sensitive readout of chemotherapy response than tumor size,” Datta said. “Mechanics are sort of disease-agnostic in that they can matter regardless of what tumor you are looking at.”

Datta hopes that doctors employ the patient models from the study to continue to grow the field’s understanding of how mechanical force can improve patient care management.

In addition to Datta, co-lead authors include Hadi T. Nia at Boston University, Ashwin S. Kumar at Massachusetts General Hospital and Harvard Medical School, and Saeed Siri at Notre Dame. Other collaborators include Gino B. Ferraro, Sampurna Chatterjee, Jeffrey M. McHugh, Patrick R. Ng, Timothy R. West, Otto Rapalino, Bryan D. Choi, Brian V. Nahed, Lance L. Munn and Rakesh K. Jain, all at Massachusetts General Hospital and Harvard Medical School.

Datta is also affiliated with Notre Dame’s Eck Institute for Global Health, the Berthiaume Institute for Precision Health, NDnano, the Warren Center for Drug Discovery, the Lucy Family Institute for Data & Society and the Boler-Parseghian Center for Rare Diseases. She is also a concurrent faculty member in the Department of Chemical and Biomolecular Engineering and a faculty adviser for Notre Dame’s graduate programs in bioengineering and materials science and engineering.

CHENNAI: Dr. Danielle Beckman is a neuroscientist whose passion for studying the brain is helping to reveal how viral infections—like COVID-19—can affect brain health and possibly lead to long-term neurological conditions such as Alzheimer’s disease.

Originally from Rio de Janeiro, Brazil, Dr. Beckman dreamed of being a writer. But after taking a college physiology course, she became fascinated with the brain. Her interest turned personal when her grandmother developed dementia, pushing her to understand what happens inside the brain during these conditions. Working at UC Davis under expert guidance, Dr. Beckman and her team created new monkey models that mimic how viruses interact with the human brain.

A new study published in Genomic Press Brain Medicine reveals that these models have shown viruses like SARS-CoV-2 (the virus behind COVID-19) can reach brain cells quickly—within just seven days—and cause inflammation, a key contributor to memory problems and brain fog.

This is different from other viruses like HIV, which affect the brain more slowly.

Dr Beckman’s findings help explain why some people experience memory issues or “brain fog” after recovering from viral infections like COVID-19. Using advanced microscopy (a way to take detailed pictures of brain cells), Dr. Beckman has identified how viruses damage brain regions related to memory and thinking.

Long COVID

Dr. Beckman is also active in the Long COVID community, supporting people who are still sick months after infection. She hopes her work will lead to real treatments, especially since there are currently no approved therapies for Long COVID-related brain symptoms.

Alzheimer’s & Beyond

In addition to studying COVID-19, her team is working on better ways to study Alzheimer’s disease. They’ve created new monkey models that more closely reflect how the disease develops in humans—something rodents (like mice) can’t do as well. These models are helping scientists test new treatments more effectively.

While the ultimate goal of this research is to find ways to prevent or reduce brain damage caused by viruses—both in conditions like Long COVID and in more traditional neurodegenerative diseases like Alzheimer’s, it is also laying the foundation for future treatments that could help millions around the world.

Introduction

NME is a rare disorder associated with multiple diseases, including glucagonoma, chronic pancreatitis, nutritional deficiency, liver diseases, and inflammatory bowel disease. About 70% of cases of glucagonoma may present with NME, therefore NME is an important visual clue for the diagnosis, enabling timely intervention.

Glucagonoma is an unusual neuroendocrine tumor, derives from the pancreatic alpha cells with an estimated incidence of 1 in 20 million,¹ most commonly affecting people in their 50s.² The main manifestations are weight loss, NME, diabetes, diarrhea, anemia, and neuropsychiatric symptoms. NME is a crucial characteristic of glucagonoma. However, many primary dermatologists lack sufficient knowledge about the disorder, leading to potential misdiagnosis and missed diagnosis. Consequently, we report a case of typical NME combined with glucagonoma diagnosed in 2024 at Dermatology Hospital of Southern Medical University, designed to strengthen the diagnosis and differentiation ability of dermatologists.

Case Presentation

The patient was a 41-year-old male who presented with erythema with erosions on both lower limbs, accompanied by malnutrition and mild itching for the past three years. The patient was diagnosed with “eczema” in the local hospital. He had been treated with topical corticosteroids for years with improvement but frequently recurred. One month ago, the lesions gradually spread all over the body, with crusted papules and polycyclic plaques with a map-like margin mainly involving the face, groin, buttocks, and extremities. And his tongue appeared beefy red and fissuring (Figure 1). No nail abnormality was found.

Figure 1 Clinical appearance. (a) Scattered erythematous seborrheic plaques on the face. (b) Bright red, swollen tongue; multiple fissures; beefy tongue appearance. (c) Well-defined erythema with raised borders and yellow crusting on both inguinal areas and scrotum. (d and e) Multiple erythema and erosion on the buttocks and knees. (f) Well-defined erythema with raised borders and yellow crusting on both ankles.

Laboratory analysis found a serum glucagon level of more than 128 pmol/L (normal range, 2 to 18 pmol/L). Anti-bp180 and anti-bp230, cortisol levels were negative. A skin biopsy was performed and showed parakeratosis, inflammatory crust, spongiosis, localized necrosis in the upper epidermis, lymphocytes infiltrating peri-follicular and peri-vascular areas, and eosinophilic infiltration (Figure 2). A contrast-enhanced abdominal computed tomographic scan revealed an enhancing pancreatic body tail mass and liver metastases (Figure 3).

Figure 2 Histological findings of plaque on the left thigh. Parakeratosis, spongiosis, localized necrosis in the upper epidermis. (HE, x 400).

Figure 3 Enhanced abnormal computed tomography scan. Showing a pancreatic body tail mass (right arrow) and intrahepatic mass (left arrow), confirming glucagonoma.

Diagnostic Evaluation

The clinical presentation was characteristic of NME, confirmed by histopathological examination of skin biopsy. In accordance with the known correlation between NME and glucagonoma, serum glucagon levels were found to be significantly elevated. Subsequent abdominal CT demonstrated a pancreatic neuroendocrine tumor, establishing the definitive diagnosis of glucagonoma. Therefore, the diagnosis of NME combined with glucagonoma was made.

Treatment with microelements such as zinc, Vitamin B, folic acid, antihistamines, and topical corticosteroids. The rash reduced slightly. However, the patient refused surgical treatment for financial reasons.

Discussion

Glucagonoma is a neuroendocrine tumor characterized by excessive proliferation of α-cells in the pancreas, with a higher prevalence in women than men. The tumor typically grows slowly and can metastasize. Due to the excessive secretion, glucagonoma syndrome occurs, which may present with NME, weight loss, diabetes, diarrhea, anemia, and neuropsychiatric symptoms.³ NME manifests as scaly, erosive, ring-shaped erythema with the formation of pustules and large blisters. Other manifestations may include nail dystrophy, cheilitis, and stomatitis.

Given the rarity of NME, reports on the condition are few both nationally and internationally, and a standardized diagnostic criterion has not yet been made. In 2018, Xuechen Cao and Yan Lu reviewed and summarized previous cases and proposed diagnostic criteria for glucagonoma.⁴ The primary diagnostic criteria(Table-1) include (1) Imaging revealing a pancreatic mass, (2) Elevated plasma glucagon levels (>1000 ng/L), (3) Typical NME manifestations, (4) A history of multiple endocrine neoplasia. Secondary criteria include (1) New-onset diabetes (fasting plasma glucose, oral glucose tolerance test), (2) low serum zinc levels and hypoaminoacidemia, (3) Unexplained weight loss and diarrhea, (4) Cheilitis or glossitis. In this case, the patient met the primary criteria of (1), (2), and (3), as well as the secondary criterion of (4), confirming the diagnosis of NME associated with glucagonoma.

Table 1 the Diagnostic Criteria and Differential Diagnosis

Given its rarity and prolonged clinical course, NME is frequently misdiagnosed as eczema. In such cases, dermatologists should maintain a high clinical suspicion for associated systemic diseases. Several conditions can present with NME-like skin rashes, including Acrodermatitis Enteropathica (AE), pemphigus erythematosus(PE), drug eruption, essential fatty acid deficiency, vitamin deficiency-related dermatitis, and pseudoglucagonoma syndrome.

AE: it is a rare, recessively inherited disorder associated with zinc metabolism abnormalities, typically presenting in infancy with symptoms such as eczema-like dermatitis, crusting, bullae, and pustules, commonly affecting the extremities and perioral areas.⁵ Additional symptoms include hair loss, diarrhea, stomatitis, photophobia, nail dystrophy, abnormal hair texture, growth retardation, and emotional disorders. Especially common in artificially fed infants, with few in adulthood.⁶ The serum zinc level is always low.⁷

PE: the lesions appear as erythematous patches, often found on the face, neck, chest, and other areas, and may have an irregular shape with unclear borders. It may also present in a linear or ring-shaped pattern, with associated vesicles and bullae. Mucosal involvement, such as oral ulcers, throat pain, and ocular inflammation, may also occur. The disease progresses rapidly, with vesicles easily rupturing to form ulcers, and lesions may spread to adjacent skin, occasionally accompanied by secondary infections. Hematoxylin-eosin stain (HE) typically shows superficial epidermal acantholysis, usually located in the granular layer or upper epidermis. Spongiosis and dermal eosinophilic infiltration can be observed, and DIF typically reveals antibodies between epidermal keratinocytes as well as scattered granular deposits of antibodies along the basement membrane zone (BMZ).⁸

Drug Eruption: it manifests in various clinical forms, with severe reactions presenting as generalized erythema, vesicles, and erosion. Drug eruption usually has a clear history of drug exposure before the onset of the rash, typically resulting from a non-anticipated inflammatory response affecting the skin and/or mucous membranes as a result of drugs entering the body through oral ingestion, inhalation, injection, suppositories, or topical absorption.² It often shows a clear response to corticosteroid therapy.

The pathogenesis of NME remains unclear. Hyperglucagonemia is believed to play a significant role, because excessive glucagon secretion induces amino acid metabolic dysregulation, culminating in hypoaminoacidemia and consequent impairment of epidermal protein synthesis. And surgical removal of glucagonomas or somatostatin analogs can control the skin rash.^6,9 Additionally, hypoaminoacidemia, micronutrient depletion, and deficiencies in essential fatty acids and zinc should also be considered, as nutritional support and topical zinc therapy have been used to improve symptoms.¹⁰ Surgical resection is considered the only curative treatment.¹¹ If left untreated, glucagonomas may metastasize to distant organs such as the liver and lungs, leading to progressive clinical deterioration and ultimately life-threatening complications. Surgical options include simple excision (for tumors <2 cm) with regional lymphadenectomy, pancreaticoduodenectomy with regional lymphadenectomy, distal pancreatectomy, and splenectomy. However, over half of glucagonomas are metastatic at diagnosis, with liver metastasis being the most common.¹² Liver transplantation is considered a potential treatment for patients with liver metastasis. Transarterial chemoembolization (TACE), radiofrequency ablation, and surgery combined may offer advantages in resecting isolated metastatic tumors. Pharmacological treatments for glucagonoma include chemotherapy, somatostatin analogs, and targeted molecular therapies.¹³ Molecular targeted therapy: Agents such as sunitinib and everolimus inhibit specific molecular aberrations within tumors, thereby significantly prolonging progression-free survival (PFS).¹⁴

Conclusion

NME mainly presents a chronic course, but the recurrent rash seriously affects the patient’s quality of life. The lesions in our case are characterized by generalized erythema with erosions, which are easily misdiagnosed as pemphigus, eczema, and drug eruption, highlighting the importance of precise imaging to exclude pancreatic tumors, when facing similar conditions. Since NME might be the only clue for the early detection of this tumor, it is very important to correctly diagnose. This requires collaborative efforts from dermatologists, endocrinologists, gastroenterologists, and oncologists. This interdisciplinary approach is essential for the timely diagnosis and management of this rare condition. All in all, this case underscores the importance of recognizing NME as a dermatologic marker for systemic malignancies, necessitating collaborative care for timely diagnosis and treatment.

Ethics Statement

The publications of images were included with the patient’s consent.

Consent Statement

The patient had given written informed consent for the publication of his clinical details. Institutional approval is not required for this case study.

Acknowledgments

The authors would like to thank the patient for participation in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by The “Set Sail” Program for Young PhD Researchers in Basic and Applied Medical Research (SL2023A04J02432).

Disclosure

The authors report no conflicts of interest in this work.

References

1. He S, Zeng W, Geng S, Jia J. Glucagonoma syndrome with atypical necrolytic migratory erythema. Indian J Dermatol Venereol Leprol. 2021;87(1):49–53. doi:10.4103/ijdvl.IJDVL_588_18

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