What is EBV Positive Mucocutaneous Ulcer?
Epstein-Barr virus (or EBV), which is commonly present everywhere, is linked to a variety of B-cell conditions that can range from mild and circumscribed to aggressive forms of lymphoma, which is a type of cancer that starts in cells that are part of the body’s immune system. Many people around the world carry this virus without showing any symptoms for their entire lives. The virus exists silently by interacting with memory B-cells, which are a type of white blood cells that remember how to fight infections.
The normal balance between the virus and your immune system keeps things under control. But any disruptions in this balance might cause an overproduction of various cell types, a condition known as lymphoproliferation. One specific condition within this range is called Epstein-Barr virus-positive mucocutaneous ulcer (or EBVMCU). This is a slow-progressing condition that affects the skin and internal lining of the body. It’s a rare occurrence and was only recently recognized as a distinct condition by the World Health Organization in 2016.
What Causes EBV Positive Mucocutaneous Ulcer?
The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is spread through saliva and tends to infect certain cells of our immune system, known as B-cells. While the virus can live in people without causing any symptoms for their entire lives, it can also lead to certain complications over time such as disorders where the body produces too many lymphocytes – a type of white blood cell.
One of the main things that can increase your risk for developing ulcers linked to EBV is a weaker than normal immune system. This can happen because of certain medications that suppress your immune response (56%), getting older which naturally weakens your immune system (40%), or having a naturally weak immune system to begin with (4%).
A number of specific drugs have been linked to these EBV-related ulcers. These include methotrexate, cyclosporin A, azathioprine, tacrolimus, TNF inhibitors, mycophenolate, and steroid creams. It’s also been suggested that the natural weakening of the immune system that happens as we get older plays a big role, especially for patients on drugs that alter the immune system.
Risk Factors and Frequency for EBV Positive Mucocutaneous Ulcer
EBV-positive mucocutaneous ulcer is often overlooked, probably because it often resolves itself and is also relatively rare amongst EBV-positive lymphoproliferative disorders – other diseases caused by the Epstein-Barr Virus. In fact, only a few cases have been reported since it was first identified in 2010. This condition is linked with both artificially-induced, natural and age-related weakened immune systems. It appears to be slightly more common in females and typically found in individuals with a median age of 66.4 years.
Signs and Symptoms of EBV Positive Mucocutaneous Ulcer
EBVMCU is a condition that often shows up as clear-cut sores in specific parts of the body. These parts can be the lining of the mouth and throat (52% of cases), the skin (29% of cases), or the digestive system (19% of cases). People with this condition usually feel the effects of these ulcers, which can lead to weight loss due to pain when swallowing and even emergencies related to the stomach. People typically don’t have whole-body symptoms, swollen lymph nodes, enlarged organs, or bone marrow complications.
The ulcers often appear in the mouth, throat, and digestive system because that’s where the EBV virus initially enters and continues to live in the body, like in the ring of lymphoid tissue in the throat (Waldeyer’s ring) and the lymphoid tissue associated with the gut. The condition’s course can go back and forth, with tissue damage from the ulcers worsening if the patient’s weakened immune system due to medication continues or increases.
- Sores in the lining of the mouth and throat (52% of cases)
- Sores on the skin (29% of cases)
- Sores in the digestive system (19% of cases)
- Weight loss because of pain when swallowing
- Belly-related emergencies
- No general body symptoms, swollen lymph nodes, large organs, or bone marrow issues
- Ulcers likely in the mouth, throat, and digestive system where the virus initially enters and stays
- Damages from the ulcers may get worse if the patient’s weakened immune system due to their medication doesn’t change or gets worse
Testing for EBV Positive Mucocutaneous Ulcer
Diagnosing EBV-positive mucocutaneous ulcer can be challenging because it can be easily mistaken for other conditions that might likewise be linked to the Epstein-Barr virus (EBV), such as diffuse large B-cell lymphoma, posttransplant lymphoproliferative disorder (an abnormal growth of cells after transplant), or classic Hodgkin lymphoma (a type of cancer). However, unlike these other conditions, this type of ulcer is localized and generally doesn’t affect the bone marrow, lymph nodes, liver, or spleen, nor is it associated with EBV getting into the bloodstream.
In order to understand this condition better, typically, a doctor would need to analyse a small tissue sample (a biopsy) using a process known as immunohistochemistry, which uses antibodies to identify diseases in the cells. Imaging tests can be valuable, and sometimes a bone marrow biopsy might be performed to ensure no other parts of the body are affected.
Treatment Options for EBV Positive Mucocutaneous Ulcer
EBVMCU, a medical condition, usually has a mild course and reacts positively to conventional management or treatments. In many instances, patients have reported full recovery either on their own or after reducing their immunosuppressive therapies, which are treatments that decrease the body’s immune system response.
However, there have been instances where the condition persists and results in more severe symptoms. These cases call for more intense treatment methods. Some case studies have found that specific targeted therapies (like CD20 or CD30-directed antibody treatment), localized radiation therapy, surgical removal, or chemotherapy have been effective. Some patients may undergo a combination of these treatments for better results.
What else can EBV Positive Mucocutaneous Ulcer be?
When it comes to diagnosing EBVMCU, a type of lymphoma, doctors would consider ruling out the following similar conditions:
- EBV-positive Diffuse Large B-Cell Lymphoma (DLBCL)
- Classic Hodgkin Lymphoma (cHL)
- Plasmablastic Lymphoma
- Post-Transplant Lymphoproliferative Disorder (PTLD)
- Anaplastic Large Cell Lymphoma
The key features of EBVMCU, like its localized nature and no mass formation, are essential to distinguish it from DLBCL despite their similar cell structure and phenotype. EBVMCU generally has clearly-defined borders with a layer of small T cells at the ulcer base, which helps discern it from the more aggressive patterns of DLBCL.
Similarities to cHL can be seen as Reed-Sternberg-like cells present in EBVMCU are CD30- or CD15-positive, although cHL is rarely found outside of the lymph nodes. If different sizes of cells are found to be EBV-positive, this leans towards EBVMCU or PTLD. Usually, in EBV-related DLBCL or cHL, only large cells are EBV-positive.
Anaplastic large-cell lymphoma could resemble EBVMCU under microscopic examination. However, this illness is a CD30-positive T-cell lymphoma and doesn’t show positivity for EBV Encoded RNAs (EBER).
What to expect with EBV Positive Mucocutaneous Ulcer
EBVMCU generally has a good outcome. In most cases, it can get better on its own or with a decrease in treatments that suppress the immune system. Some stories from individual patients have described the condition as having periods of improvement and worsening, but without getting progressively worse over time. There are also reports of persistent cases getting better with treatments like radiation, chemotherapy, or other targeted therapies.
Possible Complications When Diagnosed with EBV Positive Mucocutaneous Ulcer
The aftermath of EBVMCU, primarily relies on the site and intensity of ulcers, because they can cause severe damage to the affected tissues. Continual painful sores localized to the area like the throat can result in a condition called odynophagia, leading to weight loss. There are occurrences of a lung infection due to the intake of food or drinks into the lungs (aspiration pneumonia) and succeeding spread of infection throughout the body, associated with odynophagia as well. Additionally, ulcers can develop anywhere in the digestive system, leading to severe abdominal issues.
- Location and severity of ulcers determining outcome of EBVMCU
- Persistent painful sores can lead to weight loss
- Aspiration pneumonia and sepsis due to odynophagia
- Ulcers potentially developing anywhere in the digestive system
- Possible serious abdominal emergencies
Preventing EBV Positive Mucocutaneous Ulcer
EBVMCU, a medical condition, usually gets better on its own without needing treatment. However, if you think you might have it, it’s important to see a doctor. This is because EBVMCU can be a symptom of several different health problems, so your doctor might need to do more tests to figure out what’s causing it. Also, as more cases of EBVMCU are being found, some appear to be more severe or longer-lasting than usual. These cases need more treatment than the usual supportive care.
