What is Necrolytic Migratory Erythema?
Necrolytic migratory erythema (NME) is a distinct type of skin rash that is mainly tied to the presence of glucagonoma, which is a tumor that originates from the alpha cells of the pancreas. You are most likely to find this rash as a part of glucagonoma syndrome, which is a term for a set of symptoms including diabetes, NME, and weight loss. Sometimes, less common, NME might also show up in other medical situations, like liver disease or an issue with absorption in the intestines; in such cases, it’s referred to as pseudoglucagonoma syndrome.
As for how this rash looks, it’s notably red, it causes the surface layer of the skin to die off and it typically expands outward. Since it’s not common, it’s often mistaken for other complaints, making its detection and diagnosis a tricky process. However, since this rash often is the first sign of a pancreatic tumor, identifying and treating it early can prevent skin complications and even save lives especially if the tumor is found before it spreads to other parts of the body.
What Causes Necrolytic Migratory Erythema?
The exact reason behind a skin condition called necrolytic migratory erythema is not known. However, it’s often linked with a rare type of pancreatic tumor called glucagonoma—with about 70% of people diagnosed with this tumor showing symptoms of this skin condition first. Most glucagonomas occur spontaneously, without a clear cause. Rarely, glucagonomas along with necrolytic migratory erythema might occur with a genetic disorder called multiple endocrine neoplasia type 1 (MEN1), but this is very infrequent and only accounts for up to 3% of all glucagonomas.
There are also instances of necrolytic migratory erythema happening without a glucagonoma. When this happens, it is referred to as “pseudoglucagonoma syndrome.” This has been seen to occur alongside various health conditions, such as celiac disease (a type of intestinal malabsorption), liver cirrhosis, Crohn’s disease (a type of inflammatory bowel disease), chronic pancreatitis, and other types of cancers like small cell lung cancer, and tumors in the small intestine.
Risk Factors and Frequency for Necrolytic Migratory Erythema
Necrolytic migratory erythema, a part of the glucagonoma syndrome, is a very rare condition that only occurs in about 1 in 20 million people every year. It commonly appears in people in their fifties, with the average age of onset being 52. This condition has been diagnosed in patients as young as 15 and as old as 88.
In special cases where patients have a condition known as MEN1, this disease tends to start earlier. The condition does not favour either sex, despite previous studies suggesting that it mainly affects women. In fact, the most recent research has shown that it affects both men and women equally.
Necrolytic migratory erythema in relation to pseudoglucagonoma syndrome is even less common, and so, we don’t have data on how often it happens.
- Necrolytic migratory erythema is incredibly rare, with about 1 in 20 million people affected per year.
- The peak age for this condition is in the fifties, with the average age of onset being 52.
- The age range for diagnosed patients varies widely, from 15 to 88.
- In patients with a condition known as MEN1, the disease can start earlier.
- Previous studies suggested a female bias, but recent research shows it affects men and women equally.
- In connection with pseudoglucagonoma syndrome, this condition is even rarer, and data isn’t available.
Signs and Symptoms of Necrolytic Migratory Erythema
Glucagonoma syndrome is a condition that causes symptoms such as weight loss, diabetes, and a rash called necrolytic migratory erythema (NME). The rash is usually the first symptom and is seen in roughly 70% of patients. Most people with glucagonoma syndrome also experience symptoms of diabetes, including excessive thirst and urination, and these symptoms are reported in 80% to 94% of patients. Significant weight loss, especially in advanced stages of the disease, is another key feature.
People with NME typically have red, scaly skin lesions that grow outward. These lesions often appear in stages of healing and are more likely to be found in areas of the body where there’s more friction and pressure, such as the groin, lower abdomen, and extremities. The rash may cause intense itching or pain. It begins as red, well-defined areas and then blisters form in the center, which peel and crust over, finally healing with a darker color. As the center heals, the redness may spread outward with new blisters forming along the edges.
The rash follows a cyclical pattern, getting better and worse over roughly ten days. Physical injury can worsen or cause these lesions. It’s also possible for NME lesions to be infected, most often by Staphylococcus aureus and Candida albicans bacteria, signaled by the formation of pus-filled bumps. Misdiagnosis and ineffective treatment with antifungals or antibiotics have been reported.
- Red, scaly skin lesions
- Lesions that blister, peel, and crust
- Intense itching or pain with the rash
- Cyclical healing pattern with the rash
- Possible infection of the lesions
Approximately 30% of patients also have symptoms affecting the mouth and lips, including inflammation and cracking of the corners of the mouth, tongue inflammation, and mouth sores. Some patients also experience poor nail health. Other possible symptoms of glucagonoma syndrome include diarrhea, mental health changes (such as depression and anxiety), anemia, and a tendency towards blood clot formation. The diarrhea that’s associated with glucagonoma syndrome can be severe, affecting up to a third of patients. Some patients may also experience changes in vision and balance. The formation of blood clots is common and can lead to serious complications like deep vein thrombosis and pulmonary embolism.
Testing for Necrolytic Migratory Erythema
A thorough examination by your doctor, especially of the skin, is critical for diagnosing many diseases. If you have particular skin problems, your doctor might take multiple skin samples, preferably from the active edge of the skin problem area, because the condition sometimes only shows up in select areas.
There are a few things your doctor might test your blood for. For example, they might check the level of glucagon, a hormone in your body – if it is higher than 1000 pg/nL, this could help diagnose the condition (Glucagon usually lies between 50 and 200 pg/nL). Fasting blood sugar level or a glucose tolerance test may be used to look for diabetes, and a complete blood count can check for anemia. Deficiencies of certain nutrients like zinc, amino acids, and essential fatty acids can be assessed through your blood samples too.
Additional blood tests like Chromogranin A level, liver enzymes, bilirubin, and alkaline phosphatase could help find out if a tumour (called a neoplasm) is causing high glucagon levels. In some rare cases, a condition called MEN1 might be present, and blood insulin, calcium, parathyroid hormone, and other hormone levels might be checked.
Your doctor might also want to take images of your abdomen using a CT (computed tomography) or an MRI (magnetic resonance imaging) to look for the presence of a tumor, particularly in your pancreas as this is where the concentration of pancreatic hormone-secreting cells is the highest. Injecting a dye and taking images of the blood supplying the gut (known as selective angiography of the celiac axis) may be helpful to detect the presence of a tumor or spread of disease to the liver.
There’s another technique, called somatostatin receptor scintigraphy, that may be used for detecting spread of tumors, as most glucagonomas are positive for somatostatin receptors. This method is particularly useful if the disease has spread to lymph nodes, as they might not be detected by the dye injection method. There’s also PET-CT scanning which utilizes somatostatin analogs, a technique that has shown promise in detecting glucagonomas, even when other imaging techniques couldn’t detect them.
Treatment Options for Necrolytic Migratory Erythema
Necrolytic migratory erythema, commonly associated with glucagonoma syndrome, can be tackled through two primary approaches – surgical treatment aiming to cure and medical (or non-surgical) treatment aiming to ease symptoms.
The most effective way of treating glucagonomas, or tumors commonly located at the tail of the pancreas, and their related symptoms, is surgical excision. If there is no distant spread (metastasis) of the cancer, completely removing the tumor can typically cure the skin problems and other associated symptoms within a week. After surgery, patients will need regular check-ups including imaging and glucagon level tests after 3 and 6 months, and every 6 to 12 months subsequently.
Unfortunately, it’s quite common for the tumor to have spread to distant body parts when it’s diagnosed. The most common sites where the cancer spreads are the liver and lymph nodes around the pancreas area. Even though this makes surgical removal of the disease usually impossible, surgery to remove the original (primary) tumor can still increase survival rates, and should be attempted if possible. Thus, it’s crucial to recognize the symptoms of necrolytic migratory erythema and diagnose glucagonoma as early as possible to stop any potential spread.
Non-surgical or medical treatment becomes crucial if the cancer has already spread at the time of diagnosis, or if a patient isn’t a good candidate for surgery. Medications such as long-acting somatostatin analogs (like octreotide or lanreotide) or interferon-alpha may be used. Somatostatin analogs, which work against the effects of glucagon, have shown to help treat both necrolytic migratory erythema and other systemic symptoms associated with glucagonoma. However, the treatment needs to be continued indefinitely because the symptoms return promptly when the treatment is stopped. Other options may include chemotherapy, although it has a typically poor response rate, and biological agents like sunitinib and everolimus. Some other procedures for treating liver metastases such as liver resection and transplantation, targeted radiotherapy and chemoembolization might also be considered.
Necrolytic migratory erythema is also associated with nutrient deficiencies. Therefore, replenishing necessary nutrients like zinc, essential fatty acids, and amino acids may also help in managing the issue. Lastly, in cases where necrolytic migratory erythema isn’t caused by glucagonoma (known as pseudoglucagonoma syndrome), treatment focuses on the underlying condition. Nutritional repletion with zinc, amino acids, and essential fatty acids may be beneficial as malnutrition is common in pseudoglucagonoma syndrome.
What else can Necrolytic Migratory Erythema be?
When a doctor is trying to diagnose necrolytic migratory erythema, which is a skin condition, they will take into consideration a potential list of different conditions that might be causing the symptoms. These conditions include the following:
- Acrokeratosis paraneoplastica
- Cellulitis
- Erythrokeratoderma
- Eczematous dermatitis
- Psoriasis
What to expect with Necrolytic Migratory Erythema
Visible skin changes, such as a red, migrating rash (necrolytic migratory erythema), play an important role because they often allow for an earlier diagnosis of a condition named glucagonoma syndrome. This early identification could help prevent the disease from spreading to other parts of the body.
Unfortunately, about 50% of people having this condition may die within five years of diagnosis; however, if the condition is diagnosed early, it can significantly reduce the chances of health complications and increase the survival rate.
Possible Complications When Diagnosed with Necrolytic Migratory Erythema
Necrolytic migratory erythema (NME) doesn’t typically cause complications on its own. However, when NME is linked with a condition called glucagonoma syndrome, it can lead to certain problems such as:
- Diarrhea, which can result in dehydration
- Lack of proper nutrition in the body
- Reduced levels of aminic acid in the body (Hypoaminocdemia)
- Low levels of albumin, a protein, in the blood (Hypoalbuminemia)
- Weight loss
Preventing Necrolytic Migratory Erythema
Necrolytic migratory erythema is a skin condition that can be a sign of glucagonoma syndrome, a rare disease often associated with diabetes. To catch this condition early and provide the best chance of a successful treatment, it’s important to see a doctor as soon as possible if you notice any changes in your skin. As part of the diagnosis, the doctor will likely conduct a blood sugar test to check for diabetes.
Glucagonoma syndrome can also cause malnutrition, which means your body might not be getting enough nutrients. Therefore, maintaining a balanced diet is crucial for managing this condition. Basically, it’s important to pay attention to your nutritional status and dietary needs if you are living with this condition. If you have been diagnosed with glucagonoma syndrome, your doctor will work with you to establish an effective dietary plan to assist with your health.
