Pyogenic granuloma (PG) is a common vascular hyperplasia of the skin and mucous membranes that occurs in children and young adults.1-3 It is usually found on the face, trunk, and limbs. There are also subcutaneous4 and intravenous5,6 variants. PG is often solitary, but multiple satellite lesions may occur.7
PG was identified over a century ago and has been associated with minor trauma, chronic irritation, hormonal factors, and viral infections. To date, however, no significant causative relationships have been verified. The etiologic hypotheses have led to a number of terms used to describe PG that suggest a causative agent; these terms include botryomycosis hominis,8 granuloma telangiectodes,9 and granuloma pediculatum.10 The term pyogenic granuloma was adopted in 1925 because it was considered descriptive of the underlying process.10 Recently, the term lobular capillary hemangioma has been suggested because of the histologic appearance of the lesions.11
Epidemiology PG is common in children and young adults. In children, the mean age of onset is 6.7 years; 42% of cases occur by 5 years of age, 12% occur before 1 year of age, and 1.1% are present at birth.2 Cutaneous PG has no gender predisposition and accounts for 0.5% of all skin nodules in children.12 The incidence of oral mucosal nodules peaks in the second or third decade of life13; oral mucosal nodules occur in a 2:1 female-male ratio and are associated with pregnancy and oral contraceptive use.13 Multiple PGs usually occur in young adults but have been reported in children.13,14
Etiology and Pathogenesis The etiology of PG is unknown, but because PG regresses when potential initiating stimuli are removed, it qualifies as a vascular hyperplasia.3 Possible predisposing factors include trauma, chronic irritation, increased levels of female sex hormones, infections, viral oncogenes, and microscopic arteriovenous anastamoses.
As many as 50% of individuals with PG have a history of local trauma.10,15,16 Further, multiple PGs often develop following surgical manipulation of primary nodules.7 It has been postulated that excessive production of an angiogenic factor following trauma may be responsible for the vascular hyperplasia.17-19 However, some studies report little association between trauma and PG.2
Female sex hormones also may play a role in the pathogenesis of PG. Oral mucosal nodules occur at an increased frequency in pregnant women and in women who use oral contraceptives.13,20-22 This increased occurrence is thought to be due to an imbalance between angiogenesis enhancers and inhibitors.23 A recent study demonstrated that female sex hormones enhance the expression of angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin 1β.21 A decreased rate of endothelial cell apoptosis also was seen. Recurrence of an excised nodule is not uncommon during pregnancy, and conversely, lesions tend to resolve after childbirth.20,22,24 There is no relationship between sex hormones and cutaneous PG.
Bacterial infection is another suspected cause of PG, yet no etiologic agents have been found. Bartonella infection may manifest as a spectrum of lesions, ranging from solitary PG to widespread bacillary angiomatosis.25,26 There was a statistically significant association between PG and seropositivity for Bartonella.26 Gram-positive bacilli have also been observed on microscopic examination of PG tissue samples.25
Viral oncogenes might lead to sudden and uncoordinated growth of the dermal papillae, resulting in PG. It is hypothesized that viral infection leads to disregulation of gene repression in papillary fibroblasts.27 PG nodules may have a propensity to develop at sites of microscopic arteriovenous anastomoses.28 Consistent with this idea is the observation that the frequency of PG and the density of cutaneous vascularity is greatest in the head and neck, followed by the trunk and limbs (with vascularity greater in the upper limbs than in the lower).2,29 In addition, PGs have occurred within a nevus flammeus (port-wine stain), a type of vascular malformation.30-33
Clinical Features Commonly recognized variants of PG include cutaneous, oral mucosal (granuloma gravidarum), satellite, subcutaneous, intravenous, and congenital types. Cutaneous PG often arises as a painless, red, and crusted or ulcerated papule on the skin surface (Figure). The mean diameter of a cutaneous PG is 6.5 mm.2 The lesion develops over weeks, and growth typically stabilizes over several months.2,11,15 Eventually, it shrinks to become a fibrotic "angioma."2 Some nodules spontaneously infarct and involute. Solitary cutaneous PGs are commonly located on the head and neck (62.5%), trunk (19.7%), or limbs (17.9%), with the upper limbs involved more often than the lower.2,13
Oral mucosal nodules account for up to 70% of PGs in women.13 These lesions may develop on the gingiva, lips, or buccal mucosa.13,23 Lesions often arise during the second or third trimester of pregnancy or with the use of oral contraceptives.13,20-23 PG on the oral mucosa has a higher rate of recurrence than cutaneous PG if excised during pregnancy and often resolves spontaneously after childbirth. Mucosal PG also has been reported on the tongue,34 in the larynx,35 and on the glans penis.16,36