Introduction

Have you ever noticed a small red bump on your skin? One that bleeds easily when touched and appears to grow larger by the day. This common growth is known as a pyogenic granuloma. 

Pyogenic granuloma (also known as granuloma pyogenicum) is a common benign (non-cancerous) growth that forms on the skin or mucous membranes. Despite its intimidating name, which indicates the formation of pus or the generation of an infection, pyogenic granulomas are not caused by infection or pus. It presents itself as a bright red type of growth on the skin that appears suddenly and grows very rapidly. This can take place on any body part, such as your arms or face, and can occur after you have experienced a minor injury. Due to the delicate network of blood vessels, even the slightest touch can result in bleeding.¹ 

This article explores the pathophysiology (mechanism of disease) behind how these growths form and why they expand so rapidly. This ensures you know what this condition is, what to do if you suspect you may have it, and will help you to understand the potential future treatments that may arise. 

Causes and triggers

Pyogenic granulomas don't appear without reason, though sometimes the trigger isn't obvious. There are many reasons or triggers behind your pyogenic granuloma, which are outlined below.

Minor injuries

Everyone gets minor injuries. Whether it's a paper cut that hasn't quite healed properly, an insect bite, aggressive nail trimming or a new piercing you have been dying to get, these can lead to pyogenic granuloma. While trauma seems like an obvious trigger, research suggests that it accounts for only 7% of cases. These injuries disrupt the skin's normal healing process, which sends it into overdrive and instead of forming a neat scar, the body makes many more blood vessels and tissue.¹ 

Hormonal changes

Hormones fluctuate in everyone, whether you are going through puberty or stressed due to your nagging boss; however, pyogenic granuloma is generally more common during pregnancy when the hormone levels change dramatically, with oestrogen and progesterone soaring high. These hormones don't just affect the uterus. They also increase the level of blood vessel formation (angiogenesis) within the body. Researchers believe oestrogen may amplify the inflammatory response in gum tissue during pregnancy. Besides, the use of birth control can also cause pyogenic granuloma.²

Medications

Some medications can tip the balance toward having pyogenic granuloma. Many drugs can trigger these growths, including:²

• Retinoids 
• HIV medications like protease inhibitors 
• Antineoplastics
• Tyrosine kinase inhibitors 
• Immunosuppressive drugs, such as tumour necrosis factor-alpha (TNF-alpha) antagonists and mammalian target of rapamycin (mTOR) inhibitors 

Infections and inflammation

While pyogenic granulomas aren't infected growths themselves, infections can sometimes be the initial trigger, especially through Staphylococcus aureus (staph infection). When the body fights an infection, it releases chemicals that lead to both inflammation and blood vessel growth, which, in combination, is the perfect situation for the formation of pyogenic granuloma.^1,2

Pathophysiology of pyogenic granuloma formation

At its core, a pyogenic granuloma causes angiogenesis, which describes the growth of new blood vessels. When the skin is injured, cells release a chemical signal called vascular endothelial growth factor (VEGF), which, together with other molecules, helps new blood vessel formation to promote healing. Within normal healing, VEGF production decreases as the wound closes. However, pyogenic granulomas have uncontrollable VEGF production, and as a result, the blood vessels keep forming out of control.^2,3,4

Another key player is hypoxia, which means low oxygen. When the tissue is injured and the oxygen levels drop, the cells are stimulated to release hypoxia-inducible factors (HIFs). These quickly respond and allow the production of VEGF to occur. Within pyogenic granulomas, there is no shutdown mechanism once enough blood vessels have been formed. Inflammation also plays a key role in granuloma development. When your skin is injured, the body sends signals to the immune cells to stop the infections and thus also enables repair mechanisms to be activated. These cells then send chemical signals called cytokines, such as interleukin-1 beta (IL-1b) and tumour necrosis factor 1 (TNF-alpha). These allow the fighting of the infection and stimulate healing, but the difference in pyogenic granuloma is that the inflammatory immune response lasts longer than necessary.^1,2

Why pyogenic granuloma grow rapidly

The fast growth rate of pyogenic granulomas stems from various factors, and connects well with how it forms. 

Firstly, angiogenic factors being on overdrive is a big drive to rapid growth. High levels of growth factors, such as VEGF and fibroblast growth factors (FGFs), create an environment of constant growth signals. However, some studies show that other local and systemic factors can also contribute by releasing endogenous substances that trigger growth, such as vascular morphogenetic factors and tumour cell angiogenic factors. Moreover, balance is key to everything. A balance between all angiogenic factors, growth and cessation signals, cell growth and cell death, and a disruption to the wound healing balance also leads to rapid growth.^5,6

Elevated hormones such as oestrogen and progesterone enhance the body's response to VEGF and other growth factors, explaining why pregnancy-associated pyogenic granulomas often grow very quickly.^1,2 

Diagnosis

For doing the diagnosis, your doctor will:^1,2 

• Ask for your medical history to see which medications you are taking and whether they can be the cause of your pyogenic granuloma
• Ask you if you are pregnant
• To examine the irritation or injury on your body
• Depending on each case, the doctor may also decide to take a biopsy
• Understanding the biological mechanisms behind pyogenic granulomas helps explain the various treatment approaches available

Treatment

Medications

Medications are used to stop the cause or trigger of the pyogenic granuloma, and include:^1,2 

• Silver nitrate
• Phenol 
• Trichloroacetic acid (TCA) causes the skin to peel, helping to remove abnormal or damaged skin cells
• Eye drops (Timolol) 
• Steroid injections 
• Imiquimod skin cream 

Procedures

The following procedures are also used to treat this condition:^1,2 

• Scraping the area of the lesion and sealing it with heat
• Laser treatment
• Freezing the granuloma using cryotherapy
• Cutting the granuloma using surgical excision is the most successful treatment and has the lowest recurrence rate

FAQs

How can I prevent the risk of getting pyogenic granulomas?

Although scientists to this day aren't fully sure what causes this, it is important to avoid medications that have led to your pyogenic granuloma, avoid injuring yourself, and practice good oral hygiene to reduce your risk of getting pyogenic granulomas.

If I have a pyogenic granuloma, what do I do?

Cover your granuloma with a bandage to prevent bleeding and infection. At the same time, seek medical help.

Can it turn cancerous?

No, pyogenic granulomas do not turn cancerous or have other serious consequences, such as shortening your lifespan. However, they can easily become infected, so take all precautionary measures to prevent this and do not pick at them, as it can leave scars.

Summary

Pyogenic granulomas involve the body’s natural repair system shifting into overdrive, which can result in rapid growth of cells and can lead to bleeding. At their core, they represent dysregulated angiogenesis, persistent inflammation and disrupted wound healing.

The rapid growth that characterises this stems from various biological factors: excessive blood vessel growth, continued growth factor signalling, resistance to programmed cell death and in some cases, such as pregnancy, the involvement of hormonal amplification. Each small trauma to the growth can restart the cycle, which is why this condition can persist and recur. 

For patients, understanding that these growths represent an overgrowth of cells and not an infection or cancer is important. Although it can cause bleeding, ulceration, cosmetic concerns, and they look scary, they are completely non-cancerous and benign.