What is Angiolymphoid Hyperplasia With Eosinophilia?
Angiolymphoid hyperplasia with eosinophilia (ALHE), also known as epithelioid hemangioma, is a rare, non-cancerous skin condition that causes the growth of blood vessels, which was first identified in 1969 by doctors Wells and Whimster. The exact cause of ALHE is still unknown.
Typically, it appears as one or several small bumps or lumps, commonly on the head or neck. However, on less common occasions, these lumps might show up on other parts of the body or affect tissues beneath the skin. The main goal of treating this condition is to improve the person’s appearance and relieve any discomfort caused by these lumps.
There are numerous treatments that have been tried, though none have consistently delivered successful results.
What Causes Angiolymphoid Hyperplasia With Eosinophilia?
The causes of ALHE (Angiolymphoid Hyperplasia with Eosinophilia), a rare skin condition, are not yet entirely understood. Experts believe it might be one of two things: a growth in the blood vessels, or a response involving the lymph system.
The first theory is that ALHE could be a vascular growth. This idea is backed up by the fact that 43% of the cases had arteriovenous shunts, which is abnormal connections between arteries and veins, similar to a condition called a pyogenic granuloma. Other supportive evidence for this comes from the presence of trauma before the condition develops, like surgery, frostbite, or cuts. Also, high estrogen levels seem to contribute to this condition, which happens with some other vascular tumors during pregnancy. Moreover, recent studies found that 19 out of 20 ALHE cases had a protein, called Wilms tumor-1, within the cells of the blood vessels, which is also found in some other vascular growths. Even more, there’s a mutation of a specific receptor found in both ALHE and other non-inherited vascular anomalies. Finally, it’s suggested that an enzyme called renin might be an underlying cause for ALHE, stimulating the formation of new blood vessels and activation and movement of certain blood cells called eosinophils.
On the other hand, ALHE might be due to a lymphoproliferative disorder, which is when your body produces an excessive amount of white blood cells. Evidence for this comes from how the disease tends to reappear over time. Interestingly, a change in the T-cell receptor gene, which could potentially label this disease as a low-grade T-cell lymphoma (a type of blood cancer), has been observed in ALHE. And, a couple of previous reports noted that ALHE occurred together with a peripheral T-cell lymphoma. Additionally, a few ALHE cases showed signs of a condition called follicular mucinosis, but so far, there’s no connection made between ALHE and mycosis fungoides, another skin disorder. Of note, some cases of ALHE happened together with human herpesvirus 8 and human T-cell lymphotropic virus.
However, it’s still unclear whether ALHE is a true vascular growth with a lot of inflammation, or a lymphoproliferative process that causes a reactive blood vessel formation response.
Risk Factors and Frequency for Angiolymphoid Hyperplasia With Eosinophilia
Angiolymphoid hyperplasia with eosinophilia (ALHE) is not very common, but it’s also not considered rare. We don’t know exactly how often it occurs. Still, it happens most frequently in Asian populations, followed by White populations, and is less common amongst Black populations. This condition can affect individuals with ages ranging from 0.7 months to 91 years old – quite a wide range! On average, people are about 37 when they get diagnosed with ALHE. It’s important to note that ALHE can occur in both males and females, with no significant differences in incidence between the sexes.
- Angiolymphoid hyperplasia with eosinophilia (ALHE) is uncommon, but not rare.
- Its exact prevalence is unknown.
- The condition is mostly seen in Asians, then Whites, and less frequently in Blacks.
- The occurrence of ALHE spans a wide age range of 0.7 months to 91 years old.
- The average age of getting ALHE is around 37 years old.
- Both males and females can get ALHE, and there’s no significant difference in how often it occurs between the sexes.
Signs and Symptoms of Angiolymphoid Hyperplasia With Eosinophilia
Angiolymphoid hyperplasia with eosinophilia is a non-cancerous disease that usually appears in the skin of the head and neck, more specifically around the ear and scalp. However, it can occur anywhere on the body, including arms, legs, chest, mouth, sexual organs, and even the area around the eye. It can also affect internal organs like the heart, colon, kidneys, bones, and lungs, although this is less common. Sometimes, it can develop from arteries and take on the appearance of a blood vessel malformation.
It manifests as single or multiple pink to red-brown bumps on the skin, which can vary in size from a few millimeters to several centimeters. These bumps are often itchy, can bleed, and might be painful. Although not common, swelling of nearby lymph nodes can occur. These bumps might keep coming back, but there have also been instances where they disappeared on their own. If it develops at an early age, it tends to last longer, and its multiple spots are more likely to bleed, be painful, and itchy. A link with nephrotic syndrome (a kidney condition) has been reported in a few cases, but it isn’t well understood. When the lesions are examined with a dermoscope (a skin surface microscope), they show a mixed pattern of scattered tiny and linear blood vessels over a pink-to-red background.
Testing for Angiolymphoid Hyperplasia With Eosinophilia
When examining a patient for suspected ALHE (Angiolymphoid Hyperplasia with Eosinophilia), doctors often order blood tests. A complete blood count is performed which checks the number and health of your blood cells – in approximately 20% of ALHE cases, this reveals an increase in eosinophils (a type of white blood cell). Kidney function tests may also be administered to check for associated kidney disease.
Diagnosing ALHE usually requires a biopsy, which is when a small sample of the affected skin or tissue is taken and examined under a microscope. During this examination, doctors conduct an immunohistochemical study – a test to identify cells in tissues with a microscope by testing for specific proteins in the cells. It typically shows high levels of protein CD31 and lower amounts of proteins CD34 and factor VIII-related antigens that might be connected to the disease. Recent advancements have shown that FOSB immunohistochemistry (a test for a specific protein, FOSB) can also help diagnose ALHE by differentiating it from similar diseases. Intracytoplasmic endothelial staining of Wilms Tumor 1 (WT1, a test for another specific protein) can also be useful.
If the ALHE disease is suspected to involve internal organs, arteries, the eye socket, bones, or other parts of the body, then more detailed radiologic exams may be performed. These may include CT scans, MRIs, or ultrasounds to provide images of the internal structures and assist with the diagnosis.
Treatment Options for Angiolymphoid Hyperplasia With Eosinophilia
Angiolymphoid Hyperplasia with Eosinophilia (ALHE) is a harmless condition but can be tough to manage because of frequent recurrences, and there’s no standardized treatment method. Current treatment knowledge comes mostly from case studies and looking back at past patient experiences.
Surgery is the most commonly used treatment for ALHE, although it still has a high failure rate of 44.2% due to frequent recurrences. A specific type of surgery called Mohs micrographic surgery is suggested when the borders of the lesions are not clearly defined or when it’s important to conserve tissue. If the lesions have large skin blood vessels, a procedure called preoperative embolization may help before surgery.
Laser therapies have shown promise for patients with multiple lesions, those who want to maintain their appearance, or those who may not be good candidates for surgery. However, the recurrence rate remains high at over 50%. To improve the outcome, different types of lasers can be used together, along with maintenance treatments to prevent recurrence.
Other treatments that have shown promise include photodynamic therapy, where light is used to kill cancer cells, cryotherapy which freezes off the lesions, Electrodesiccation which dries out and destroys the tissue, as well as radiotherapy that uses radiation to kill cancer cells. Several other interventions like injecting certain drugs into the lesions (sclerotherapy), applying high-frequency radio waves (radiofrequency ablation), or using a combination of both have shown improved outcomes in a handful of individuals.
Some oral and systemic medications have been used as well, like corticosteroids, isotretinoin, dapsone, pentoxifylline, methotrexate, and thalidomide, but these have generally resulted in high failure rates. Another drug, Mepolizumab, which targets a specific protein involved in inflammation, has been used in patients with ALHE connected with abnormally high eosinophils levels in the blood, resulting in reduced itching and fewer lesions.
Recent guidelines have also recommended the drug propranolol, either on its own or prior to surgery, to reduce the size or number of lesions.
Topical treatments (applied to the skin) like timolol appear to have had some success, but recurrence rates remain high. Other local treatment options include corticosteroids, imiquimod, topical tacrolimus, or even an injection of a medication known as interferon alpha-2b, but these have resulted in varied outcomes.
What else can Angiolymphoid Hyperplasia With Eosinophilia be?
It’s important to remember that ALHE can look like other medical conditions, so it’s crucial to make an accurate diagnosis. Some of the conditions that could be mistaken for ALHE include:
- Kimura disease: Common in young Asian men, it creates solitary or many large subcutaneous masses with a deeper localization, often in the salivary glands. It may also present with regional lymphadenopathy, blood eosinophilia and elevated IgE. It can also be associated with Nephrotic syndrome.
- Pyogenic granuloma: This condition appears as an eruptive papule that is sometimes eroded or ulcerated, with specific histological features different from those of ALHE.
- Nodular Kaposi sarcoma: It can appear similar to ALHE on the surface. However, its histopathological characteristics usually provide a clear distinction.
- Angiosarcoma: Especially in its epithelioid variant, angiosarcoma shows rapid growth and aggressive course. Its histological characteristics, such as vigorous mitotic activity, polymorphism, and nuclear hyperchromasia, can help differentiate it from ALHE.
- Epithelioid hemangioendothelioma: Its unique histological features, such as the presence of myxohyaline stroma, lack of lymphoid or eosinophilic infiltrate, and the presence of mitoses and nuclear atypia, can help in making a correct diagnosis.
- Granuloma faciale: Often presenting as a red-brown plaque on the face, its histological features are different from those of ALHE and can therefore help in diagnosis.
To make the correct diagnosis, doctors need to be aware of these possible confusions and carefully consider the unique characteristics of each condition.
What to expect with Angiolymphoid Hyperplasia With Eosinophilia
Angiolymphoid hyperplasia with eosinophilia is a condition that often lasts for several years and can come back, or recur, in more than 40% of cases after treatment. People who develop this condition at a young age, those who’ve had it for a long time, and those who have multiple lesions, or areas of damage, tend to experience recurrence more frequently. In some cases, the condition might get better on its own.
Although, there have been some cases where there were abnormal changes in the genes of T-cells (a type of white blood cell that fights infections) and ‘monoclonality’ (a condition where all the cells are identical), there’s currently no firm evidence to suggest that this condition can turn cancerous or behave in a malignant way.
Possible Complications When Diagnosed with Angiolymphoid Hyperplasia With Eosinophilia
Angiolymphoid hyperplasia with eosinophilia is a non-serious condition. While it has been linked to kidney disease in some reports, this is quite rare. Depending on the location of the condition, you might experience different complications. For instance, it can cause rectal bleeding if found in the colon. If occurring in the area around the eyes, it may lead to bulging of the eyes, seeing two images when there should only be one, and blurred vision. Angiolymphoid hyperplasia affecting the arteries could press onto nearby nerves, leading to numbness or abnormal sensations in the area it affects, as reported in a case where the ulnar nerve was affected. Moreover, it can completely block an artery leading to long-term problems due to insufficient blood supply. In the case of one patient with research-backed records, the condition occurred in the heart and led to irregular heart rhythm incidents.
Common Complications:
- Rectal bleeding if located in the colon
- Eye bulging, double vision, and blurred vision if located in the orbital area
- Numbness or abnormal sensations if it presses on nearby nerves
- Long-term blood supply issues if it completely blocks an artery
- Irregular heart rhythm if it occurs in the heart
Preventing Angiolymphoid Hyperplasia With Eosinophilia
Patients who have ALHE, which is a chronic skin condition, should be prepared that it could stick around for a long time or even come back after they’ve been treated. However, it’s important to remember that this condition is not harmful or life-threatening. It would also be useful to understand different treatment options available for this condition. This way, patients can actively participate in deciding what treatment route they’d prefer to take for their care.
