A hemangioma is a benign tumor made up of blood vessels. Symptoms of hemangioma may be present at birth or appear during adulthood. Timolol is often used as the treatment of hemangioma.

Hemangioma

A. JABBAR DENTAL CLINIC KARACHI

Sadia Khan

Overview

Also called &ldquo;strawberry marks&rdquo;, hemangiomas are benign growth of blood vessels. They appear as bright red birthmarks, either at birth or in the first two weeks of life. Hemangiomas are the most frequent benign tumour in infancy. They are also referred to as: 
&nbsp;

<ul>
	<li>Hemangiomas of infancy</li>
	<li>Infantile hemangiomas (IH) 
	&nbsp;</li>
</ul>

Infantile hemangioma is childhood&#39;s most common benign vascular tumour, affecting approximately 4% to 5% of newborns<a href="#accordion">[2]</a>. They are more prevalent in babies born to elderly mothers. Moreover, it is more common in females than males, with a female-to-male ratio of up to 5:1<a href="#accordion">[2]</a>. 
&nbsp;

Hemangiomas typically appear as red or blue-purple rubbery-looking bumps on the skin. An estimated 1%&ndash;2% of hemangiomas are visible at birth<a href="#accordion">[1]</a>. They can appear at any place on the body, with 60% occurring on the head and neck<a href="#accordion">[2]</a>. Whereas in 25% of cases, the lesions appear on the trunk, and in 15% of cases they appear on the extremities<a href="#accordion">[2]</a>.

in addition to the skin and liver, hemangiomas can present on other parts of the body,for example: 
&nbsp;

<ul>
	<li>Lungs</li>
	<li>Colon</li>
	<li>Kidneys</li>
	<li>Brain 
	&nbsp;</li>
</ul>

Hemangiomas typically grow for some time before disappearing without treatment. They don&rsquo;t normally cause problems in infants. However, in some cases, they may be painful and also prone to bleed. Moreover, based on their size and location, they may be disfiguring. 
&nbsp;

Note: If a hemangioma impairs vision, breathing, or other functions, treatment should be sought immediately. 
&nbsp;

Hemangiomas can occur anywhere on the body. There are three main types of hemangiomas - superficial, deep, and mixed<a href="#accordion">[2]</a>. 
&nbsp;

<ul>
	<li>Superficial Hemangiomas - These lesions only involve the superficial dermis. They appear as bright red lesions with a raised, lobulated surface. 
	&nbsp;</li>
	<li>Deep Hemangiomas - Also called subcutaneous hemangiomas, these involve the reticular dermis and/or subcutis layer. They appear as bluish-purple swellings with a smooth surface. 
	&nbsp;</li>
	<li>Mixed Hemangiomas - These hemangiomas have features of both superficial and deep. 
	&nbsp;</li>
</ul>

Hemangiomas are of several types. The 3 most common types are: 
&nbsp;

<h5>1. Capillary Hemangiomas</h5>

This is the most common type of hemangioma and appears on the outer surface of the skin. When it appears on the skin, it is also called &ldquo;superficial&rdquo;. It is comprised of a high number of tightly packed small capillaries, held together by connective tissue. 
&nbsp;

<ul>
	<li>&nbsp;Strawberry Hemangioma (Infantile hemangioma)</li>
</ul>

These appear as red bumps on the skin that can grow to one-quarter to two inches in size. Approximately 12% of babies are affected by infantile hemangiomas in the first year of life<a href="#accordion">[8]</a>. Strawberry hemangiomas grow rapidly and then shrink and disappear. 
&nbsp;

<ul>
	<li>Cherry Hemangiomas</li>
</ul>

Cherry hemangiomas are small, raised red blood vessel growths that mostly develop on the torso. They are quite common in adults, especially as they age. Cherry hemangiomas usually appear in groups of a few to dozen. 
&nbsp;

<h5>2. Cavernous Or Deep Hemangiomas</h5>

Cavernous hemangiomas form in the deepest layers of the skin, often around the eyes.

<ul>
	<li>Cavernous hemangiomas are frequent on the surface of the eye, eyelids, and eye socket.</li>
	<li>Whenever they first appear on or under the skin, they look like clusters of big blood vessels that can range in hue from dark red to blue.</li>
	<li>These hemangiomas can obstruct eye growth and result in vision problems such as glaucoma, amblyopia, and cataracts.</li>
	<li>Unlike capillary hemangiomas, the blood vessels are not as closely packed and the caverns, or spaces between them, are filled with blood.</li>
	<li>These masses frequently appear in groups in the brain, and invariably on one side exclusively. The condition is quite prevalent.</li>
</ul>

<h5> 
3.&nbsp;Liver Hemangioma</h5>

A liver hemangioma (hepatic hemangioma) is a benign tumour of the liver. It is composed of clumped, deformed blood vessels supplied by the hepatic artery. The presence of a liver hemangioma doesn&#39;t indicate something is wrong in your liver, and it won&#39;t harm your liver. 
&nbsp;

Signs and Symptoms

Hemangiomas do not normally cause signs and symptoms during or after their formation. However, they cause symptoms if they grow large, originate in a sensitive area, or if there are several hemangiomas. 
&nbsp;

<h5>Hemangiomas Of The Liver</h5>

The following are the most prevalent symptoms:

<ul>
	<li>Pain in the right upper abdominal quadrant.</li>
	<li>Bloating</li>
	<li>A lack of appetite or feeling of fullness</li>
	<li>Nausea and vomiting 
	&nbsp;</li>
</ul>

<h5>Hemangiomas Of Skin</h5>

A hemangioma can be present at birth, but it is more common in the first few months of life.

<ul>
	<li>Hemangiomas of the skin mostly occur as tiny red marks or lumps. They appear as burgundy birthmarks as they advance. </li>
	<li>It starts as a leveled red scratch on the body, most commonly on the chest, face, scalp, or back. A child normally has just one scratch. Few infants may have multiples, especially if they are part of multiple births.</li>
	<li>Throughout your baby&#39;s first year, the red scratch transforms speedily into a spongy, rubbery-looking lump that protrudes from the skin. The hemangioma then goes into a dormant state and gradually fades away, typically by age 5 or 10. 
	&nbsp;</li>
</ul>

<h5>Cavernous Hemangioma</h5>

Internal hemangiomas induce symptoms specific to the affected organ. Symptoms of cerebral cavernous hemangiomas include:

<ul>
	<li>Double vision or blurred vision</li>
	<li><a href="https://merisehat.pk/disease/absence-seizures">Seizures</a></li>
	<li>Speech slur</li>
	<li>Limb paralysis or weakness 
	&nbsp;</li>
</ul>

Note: If the hemangioma changes colour, bleeds, blocks vision, or affects the ability to breathe or eat, contact a healthcare professional immediately. 
&nbsp;

Causes

The cause of hemangiomas is unknown. A hemangioma is a collection of additional blood vessels that make a thick cluster. It is unknown what induces the vessels to the group. 
&nbsp;

<h5>1. Hemangioma On The Skin</h5>

Hemangiomas of the skin are formed when blood vessels proliferate abnormally in one area of the body. Medical specialists are not certain why blood vessels cluster with each other in this way. However, they think it&#39;s triggered by specific proteins formed in the placenta during gestation. 
&nbsp;

<h5>2. Hemangioma On The Liver</h5>

Hepatic hemangiomas develop within and on the surface of the liver. These may or may not be linked to infantile hemangiomas. Non-infantile hemangiomas of the liver are believed to be estrogen-sensitive.

Many women are recommended replacement estrogen during menopause to alleviate signs and symptoms induced by a decrease in their general estrogen levels. Additional estrogen can promote the development of liver hemangiomas. Likewise, pregnancy and, in a few cases, oral contraceptive pills can cause hemangiomas to grow in size. 
&nbsp;

<h5>3. Cavernous Hemangiomas </h5>

Most cavernous hemangioma malformations are hereditary. A mutation in any of the genes can cause this. Other factors include

<ol>
	<li>&nbsp;Developmental venous anomaly (DVA)</li>
	<li>&nbsp;Radiation treatment to the brain or spine. 
	&nbsp;</li>
</ol>

Diagnosis

A medical professional can normally detect a hemangioma by just looking at it. Pediatric dermatologists are specialists in the diagnosis and treatment of hemangiomas. During a physical test, your healthcare provider can perform a visual diagnosis. Depending on where the hemangioma is located, the doctor can perform tests to determine how far it extends beneath the skin and whether it influences any internal organs. The following tests are carried out: 
&nbsp;

<ul>
	<li>
	<h5>Skin Biopsy</h5>
	</li>
</ul>

If there are any doubts, a skin biopsy can also be done to diagnose hemangioma. 
&nbsp;

<ul>
	<li>
	<h5>Imaging Studies</h5>
	</li>
</ul>

Imaging studies are recommended to verify the detection and determine the degree of deep infantile hemangiomas without modifications on the surface. Hemangiomas on organs may be detected only by an imaging test. Such as:

<ul>
	<li>Ultrasonography</li>
	<li>Computed tomography (CT)</li>
	<li>Magnetic resonance imaging (MRI) 
	&nbsp;</li>
</ul>

Imaging tests are done to rule out any potential complications and to distinguish proliferating IH from other tumours. They are usually discovered by chance in a few cases. 
&nbsp;

<h5>Some Diseases Associated With Hemangiomas</h5>

1. PHACE Association

Large infantile hemangiomas are sometimes associated with the PHACE syndrome. Every letter represents a condition: 
&nbsp;

P &ndash; Posterior fossa malformation

H &ndash; Hemangioma

A &ndash; Abnormal arteries in the brain or big blood vessels near the heart

C &ndash; Coarctation of the aorta

E &ndash; Eye problems 
&nbsp;

An &#39;S&#39; is sometimes added to PHACE, which stands for sternal clefting/supraumbilical raphe, a condition in which the breastbone does not develop correctly or there is scarring in the skin over the chest.

A big hemangioma, generally in the head or neck, occurs seldom in conjunction with one or more of these diseases in the brain, heart, eye, or blood vessels. 
&nbsp;

2. Sturge-Weber Syndrome (SWS)

&nbsp;It is a neurocutaneous syndrome characterized by the presence of facial port-wine hemangiomas in the trigeminal nerve distribution area, as well as brain vascular malformation (e.g., leptomeningeal angioma). It might occur with or without glaucoma.<a href="#accordion">[3]</a> 
&nbsp;

3. Klippel&ndash;Trenaunay Syndrome

It is defined by a combination of capillary abnormalities (hemangiomas), venous varicosities, and bony- or soft-tissue hypertrophy.<a href="#accordion">[4]</a> 
&nbsp;

Treatment

Most infantile hemangiomas heal on their own, so treatment is unnecessary, whereas doctors must treat complicated infantile hemangiomas. If a hemangioma interferes with vision or triggers other issues, treatment options are available, which include medications or surgery: 
&nbsp;

<h5>Beta-Blockers</h5>

<ul>
	<li>Oral Propranolol</li>
</ul>

Oral propranolol (2 mg/kg/day) is a first-line therapy for hemangioma. In 2014, the US Food and Drug Administration (FDA) permitted hemangeol (oral propranolol hydrochloride) for hemangiomas.<a href="#accordion">[5]</a> 
&nbsp;

<ul>
	<li>Timolol</li>
</ul>

Timolol is a topical beta blocker. It is used to treat small infantile hemangiomas that appear on the surface and are uncomplicated. They may also play a role in the treatment of small ulcerated hemangiomas. When used correctly and under the supervision of a medical professional, this medicine is normally considered harmless. 
&nbsp;

<h5>Corticosteroids</h5>

The doctors can administer intralesional and topical corticosteroids to cure little focal lesions. They may be injected into a hemangioma to reduce its growth and stop inflammation. Corticosteroids may be a choice for children who do not respond to beta-blockers or are unable to use them. However, they are associated with side effects such as thinning of the skin and poor growth.

Prednisone and prednisolone are no longer commonly used systemic steroids. They may, however, have a role for those people who are unable to take other drugs, for example, beta-blockers, which are more commonly used. 
&nbsp;

<h5>Medicated Gel</h5>

Becaplermin (Regranex) is a costly medicated gel that has been used off-label in a few types of research to cure firmly established ulcerated hemangiomas. Individuals who receive it regularly are at risk of developing cancer. Discuss the risks with your medical professional. 
&nbsp;

<h5>Surgical Excision</h5>

To avoid complications, surgical excision may be advised if the hemangioma is small enough. 
&nbsp;

<h5>Laser Surgery</h5>

Occasionally, small hemangiomas or sores on a hemangioma can be treated with laser surgery. It can be employed to remove hemangiomas on the skin&#39;s top layers. In a few instances, a medical professional may employ laser treatment to lessen redness and enhance the appearance. 
&nbsp;

<h5>For Internal Organs</h5>

The majority of internal hemangiomas do not require treatment. Healthcare providers may advise treatment if a hemangioma compresses an organ, impairs body functions, or induces discomfort, ache, or other physical signs.

Surgical removal of hemangioma is a common treatment. Medical professionals will get rid of a problem-causing brain hemangioma whenever feasible. If absolute removal is not attainable, they may employ a kind of focused radiation.

Medical professionals remove liver hemangiomas only if the signs are severe or the benign tumour is advancing rapidly.

A few hemangiomas come back following removal, in contrast to other benign growths that do not. 
&nbsp;

1. Hemangiomas&#39; most prevalent complication is ulceration which occurs in 10% of cases<a href="#accordion">[2]</a>. An ulcer is a sore or wound on the skin that develops over a hemangioma. Ulcerated hemangiomas might be quite painful and must be treated in order to heal. 
&nbsp;

2. Other issues may emerge depending on the origin of the infantile hemangioma: 
&nbsp;

<ul style="list-style-type:disc">
	<li>Vision Problems &ndash; when situated on or near the eye</li>
	<li>Feeding Problems &ndash; when found within or around the mouth</li>
	<li>Breathing Difficulty &ndash; when positioned in the airway</li>
	<li>Infections</li>
	<li>Large Infantile Hemangiomas &ndash; particularly those in the liver, can induce heart failure</li>
	<li>Infantile Hemangiomas Associated With PHACE Syndrome &ndash; have the potential to disrupt many bodily processes. 
	&nbsp;</li>
</ul>

Hemangiomas are more common in female babies, white people, and preterm babies. 
&nbsp;

Hemangiomas can run in families in certain situations. They can also appear on their own, implying that the illness may have a hereditary component. Because the actual etiology of hemangiomas of the skin is unknown, there is no strategy to prevent them. Growth, on the other hand, can be slowed by using topical therapies. However, the majority of hemangiomas undergo complete involution. 
&nbsp;

Identification of Novel Potential Biomarkers in Infantile Hemangioma via Weighted Gene Co-expression Network Analysis.

One of the most prevalent benign tumours in children is infantile hemangioma (IH). Even though some IH can resolve without treatment, certain hemangiomas may not recede and instead worsen, making them challenging to treat in therapeutic settings. As a result, discovering a new treatment for IH is vital.<a href="#accordion">[7]</a>

Using microarray analysis, researchers identified differentially expressed genes (DEGs) in hemangioma tissues. Three genes (APLN, APLNR, and TMEM132A) were discovered as hub genes that were persistently abundantly expressed in hemangioma tissues independent of stage.

These hub genes may influence IH development via endothelial cell proliferation, sprouting angiogenesis, and apelin signalling. These genes may help us understand the process of IH and may be anti-angiogenesis treatment targets for IH. 
&nbsp;

Key Points

<ul>
	<li>Also called &ldquo;strawberry marks&rdquo;, hemangiomas are benign growth of blood vessels. They appear as bright red birthmarks, either at birth or in the first two weeks of life.</li>
	<li>Hemangiomas are the most frequent benign tumour in infancy</li>
	<li>Infantile hemangiomas fade and disappear during childhood. Certain medications can help them fade faster.</li>
	<li>Some hemangiomas can lead to complications due to their size or location in the body. 
	&nbsp;</li>
</ul>

[1] Léauté-Labrèze C, Prey S, Ezzedine K. Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad dermatology Venereol. 2011;25(11):1245–53.

[2] Chamli A, Aggarwal P, Jamil RT, Litaiem N. Hemangioma. In: StatPearls [Internet]. StatPearls Publishing; 2022.

[3] Chen L, Wu J, Xu M, Chen N, Yang Y. Sturge-weber syndrome. Ann Dermatol. 2011;23(4):551–3.

[4] Deka JB, Deka NK, Shah M V, Bhatnagar N, Nanni AL, Jimenez F. Intraneural hemangioma in Klippel--Trenaunay syndrome: role of musculo-skeletal ultrasound in diagnosis—case report and review of the literature. J Ultrasound. 2020;23(3):435–42.

[5] Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo J-B, Taïeb A. Propranolol for severe hemangiomas of infancy. Vol. 358, The New England journal of medicine. United States; 2008. p. 2649–51.

[6] Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting  complications and treatment. Pediatrics. 2006 Sep;118(3):882–7.

[7] Xie B, Zhou X, Qiu J. Identification of novel potential biomarkers in infantile hemangioma via weighted gene co-expression network analysis. BMC Pediatr. 2022;22(1):1–11.