Introduction

Definition of pyogenic granuloma

The term pyogenic granuloma (PG), or granuloma pyogenicum, describes a common, acquired, benign vascular tumor from tissues such as the skin and mucous membrane.^1,2 It can occur at any age and affect the face, trunk, and limbs.^3,4 As for the latter, it can be found most commonly in the oral cavity.¹ In rare cases, it can also occur at other sites in the gastrointestinal tract.¹ There are also subcutaneous and intravenous variants. 

PG can occur as a single lesion or multiple satellite lesions.⁴ PG has a 1 to 1.2 female-to-male ratio as reported in reviews. Male patients with both cutaneous and mucosal variants tend to develop the condition earlier, typically from childhood to their late twenties. Conversely, women between the ages of thirty and forty are more likely to be affected. Additionally, a pediatric study found that males tended to be diagnosed at a younger age, with an average age of 6 to 10 years.^14,15 An accurate scientific term for this condition is lobular capillary hemangioma (LCH). The disorder has been associated with minor trauma, chronic irritation, hormonal factors, and viral infections for over a century. As of yet, no significant causative relationship has been determined.⁴

Causes and risk factors

Numerous factors may contribute to the occurrence of this disease, but no one is certain of the cause. In addition, studies of specific angiogenic factors and signal transduction pathways have not identified a single pathway contributing to the pathogenesis of the lesion. There is evidence to suggest that neovascular capillary proliferation is the result of an imbalance between proangiogenic and antiangiogenic factors, which leads to neovascular, friable, and lobulated capillaries to multiply rapidly. However, only 7% of these lesions can be directly connected to trauma.¹ 

Female sex hormones may also influence the pathogenesis of PG. The incidence of the disease peaks later in women's lives, usually during childbearing years.⁴ Moreover, some medications, such as oral contraceptives, retinoids, gefitinib, capecitabine, and afatinib, have been linked to this condition.² Generally, tumours are solitary lesions, but there have been reports of multiple grouped or disseminated lesions. 

Treatment for melanoma with selective BRAF inhibitors, such as vemurafenib and encorafenib, may cause multiple disseminated tumours on the skin.⁵ Furthermore, some targeted oncological therapies, including epidermal growth factor receptor inhibitors (EGFRI), mitogen-activated protein kinase inhibitors, and rituximab, have been shown to cause multiple periungual PG.² 

Common symptoms and diagnosis

The lobular capillary hemangioma usually starts as a small papule, then undergoes a variable, sometimes rapid exophytic growth phase, eventually stabilising in size. There are several variations in color, including red, reddish-brown, and purple. The diameter varies from a few millimeters for small lesions to 4 cm in diameter for larger lesions.¹⁰ Lesions are usually solitary, but satellite lesions can form nearby, and sometimes, disseminated lesions are noted. Mature lesions are polypoid or pedunculated and have a "collarette" of scale at the base of the lesion.¹ 

In spite of the ease of diagnosis of lobular capillary hemangioma based on a history and examination, there are certain red flag diagnoses that should be considered. These include lesions such as amelanotic melanoma, squamous cell carcinoma, basal cell carcinoma, angiosarcoma.¹ 

Importance of effective treatment 

Ulcers and bleeding are the most common causes of lobular capillary hemangiomas, which require treatment. Currently, there are no accepted standards of care for the treatment of these lesions due to the limited number of clinical trials.¹ While treatments for PGs exist, they differ in success rates. Despite all the treatment options available, the main challenge is the high rate of recurrence, which ranges from 3.7% to 43.5%.⁶ The treatment of PG can be divided into two categories: non-surgical and surgical. However, comparing the recurrence rates between the two showed no significant differences.⁶

Non-surgical treatment approaches

Non-surgical treatment includes topical medication, intralesional injections, cryotherapy, electrocautery, or chemical cautery with silver nitrate without excision, and laser therapy. Some of the lasers used include pulsed dye lasers (PDL) and CO2 lasers, as well as the 1,064 nm Nd:YAG laser on its own or in combination with surgical intervention.^7,8,9 As shown in one of the studies, cryotherapy is an easy-to-perform, cheap treatment of PG with no significant side effects and scarring. It could be one of the first-line therapeutic modalities used as it is much easier than excision and curettage, and cheaper than laser. Moreover, in the same study, 7.8% of the lesions disappeared after one treatment, 88.1% after one or two treatments, 96.2% after one to three treatments, and all lesions after one to four treatments. The cosmetic result was excellent in 94% of the patients. However, further research is required in this area.⁷

Additionally, topical medications and intralesional injections have been used with variable results. These include topical imiquimod cream, alitretinoin gel, timolol, propranolol, and even phenols for periungual lesions.¹ It has been reported that intralesional use of corticosteroids and sclerosants, such as ethanolamine oleate, sodium tetradecyl sulfate, polidocanol, and bleomycin for sporadic patients has been beneficial.¹ Although there is a higher recurrence rate after treatment in cases of pregnancy-induced lobular capillary hemangiomas or those caused by medication, it is recommended to discontinue the medication.¹ Finally, among the different treatments mentioned, cryotherapy with liquid nitrogen had the lowest overall recurrence rate of 1.62%.¹

Surgical treatment approaches

There are many surgical treatment approaches, including surgical excisions and curettages/shave excisions, etc. Since complete excisions have a lower recurrence rate and provide excellent specimens for histopathologic analysis, and are performed under local anesthesia, they are preferred for non-visible locations. Sessile or recurrent lesions are best excised with suturing, which results in less postoperative bleeding and a lower recurrence rate after surgery.¹ In a case study, electrocautery was used to remove a lesion under local anesthesia for a 45-year-old female patient. Follow-up examinations were conducted after the procedure, and no recurrences were found, nor was there any scarring, and the healing process was deemed satisfactory.¹¹

A study used curettages to treat PG, and 94% of the patients were satisfied with the results. Curettage also has the advantage of requiring fewer treatment sessions, producing better cosmetic results, and having the ability to confirm the diagnosis histologically.⁸ Moreover, the procedure is much simpler than excision, cheaper, and more widely available than laser treatment.⁸ Compared to other approaches, curettage has the advantage of differentiating and removing friable abnormal tissue from normal surrounding tissue with the least amount of damage to normal tissue.¹² Finally, comparing the treatments mentioned in this group, Surgical excision had the lowest recurrence rate among them, with a crude recurrence rate of 2.94%.¹

Comparing surgical vs. non-surgical approaches

While there is a limited number of clinical trials accepting the standard approach of care for PG treatment, more investigation should be conducted in this matter. Several factors must be considered, such as gender, the size of the lesion, cost, and the age of the patient. For instance, the surgical excision proved highly effective. It stands out from methods such as lasers and injectables, which exhibit varied success rates requiring multiple treatment sessions. Meanwhile, curettage and shaving are more cost-effective but have a good cosmetic outcome. In general, PG management strategies require more comparative research due to a diversity of studies and varying levels of evidence.¹³

Summary

A pyogenic granuloma is typically a benign vascular tumor affecting the skin or mucous membrane, associated with trauma, hormonal changes, or medications. It appears as a rapidly growing red, reddish-brown, or purple lesion that may ulcerate and bleed easily, requiring treatment due to high recurrence rates. There are a variety of non-surgical treatments that have varying success rates, including cryotherapy, topical medications, intralesional injections, and laser therapy. Surgical techniques such as excision, curettage, and electrocautery provide definitive treatment at a lower recurrence rate and allow histological confirmation. Although surgical excision is still the most effective treatment, non-surgical methods may be more suitable for patients seeking less invasive treatments. Lastly, more comparative research is needed to determine an optimal management strategy based on the characteristics and preferences of the lesions.