Pediatric Pyogenic Granuloma

Pyogenic granulomas (PGs) are benign vascular lesions that occur most commonly on the acral skin of children.[1, 2] The term pyogenic granuloma is a misnomer. Originally, these lesions were thought to be caused by bacterial infection; however, the etiology has not been determined. The histopathologic appearance is fairly characteristic; the lesion is, in fact, a lobular capillary hemangioma.[3]

Recognition of pyogenic granuloma as a clinically polypoid or exophytic circumscribed lesion is of importance to the clinician and pathologist because this feature distinguishes pyogenic granulomas from most malignant vascular tumors. Although pyogenic granulomas may be multiple (especially on the skin) and necrosis is common, invasion of adjacent structures is not observed. The lesions grow rapidly and are extremely vascular, frequently bleeding either spontaneously or after minor trauma.[4] They are usually easily treated with surgical removal but may recur.

Uncommon variants include pyogenic granuloma with satellitosis,[5, 6, 7] intravenous pyogenic granulomas,[8] subcutaneous pyogenic granulomas,[9, 10] and eruptive pyogenic granulomas.[11, 12, 13] Satellite lesions of smaller pyogenic granulomas may develop at the same time as the primary lesion or may occur after attempted treatment of the primary lesion. See the images below.

Although most patients (74.2%) do not have a history of trauma or predisposing dermatologic conditions, in many cases, a history of recent trauma at the site is present. Large numbers of lesions may occur following damage to diffuse areas skin by burns or other trauma.[14, 15] A nitric oxide synthase–dependent mechanism is thought to contribute to angiogenesis and the rapid growth of pyogenic granulomas (PGs). They are benign vascular proliferations, but the specific pathophysiology of these lesions is unknown.

Originally, pyogenic granulomas (PGs) were thought to be caused by bacterial infection; the etiology has yet to be determined. Postulated etiologies include viral, hormonal, and, more recently, angiogenic factors.

Pyogenic granulomas have been evaluated for the presence of human papillomavirus (HPV) because warts occur in similar age groups and sites. Lesions were tested for HPV 6, 11, 16, 31, 33, 35, 42, and 58. No viruses were present.

Recurrent pyogenic granuloma with satellitosis is an uncommon variant. In one patient with recurrent pyogenic granuloma with satellitosis, Warthin-Starry staining of the lesions revealed clumps of dark bacilli as found in patients with bacillary angiomatosis.[5] An indirect immunofluorescence assay showed elevated immunoglobulin G antibodies against Bartonella (Rochalimaea) henselae. The patient did not present an obvious risk for human immunodeficiency virus (HIV) infection or immunosuppression; no antibodies against HIV-1 and HIV-2 were found. Recurrent pyogenic granulomas with satellitosis may be a localized variant of bacillary angiomatosis.

US frequency

Pyogenic granulomas (PGs) account for 0.5% of skin lesions in infants and children and are also found in the oral mucosa in 2% of pregnant women.

Race

No substantial difference in incidence is found between races.

Sex

One study of 178 patients younger than 17 years reported the male-to-female ratio as 3:2.[16] In adults, pyogenic granulomas are more common in females because of pregnancy-related lesions.

Age

Pyogenic granulomas are most common in the first 5 years of life.[17]

Prognosis is excellent after simple removal and wound care. Most pyogenic granulomas (PGs) are asymptomatic except for mild tenderness and a tendency to bleed with little or no trauma. They are benign and easily treated. Rarely, pyogenic granulomas in unusual sites such as the intestines may result in significant bleeding[18, 19, 20] or other major complications.[21]

Patients with pyogenic granulomas (PGs) usually seek care because the lesion has grown rapidly and bleeds easily. Patients or parents may be concerned because the lesion bleeds with little or no trauma; they are frequently concerned that the rapid growth and bleeding may indicate a malignancy.

Important questions include the following:

• Does the history include trauma at the site prior to development of the lesion? Pyogenic granulomas may occur following minor physical trauma or burns.

• How long has the lesion been present? Most pyogenic granulomas develop rapidly. The mean duration at the time of diagnosis is approximately 3 months. If the lesion has been present longer than 6 months, the possibility of cutaneous malignancy increases.

• Does the lesion bleed easily? Almost all pyogenic granulomas bleed easily. If the lesion does not bleed with light rubbing, a diagnosis of pyogenic granuloma is unlikely.

• What therapy has been used recently? Nevi, warts, or other lesions may have been treated with caustic agents or cryotherapy prior to referral. Such therapy may markedly change the appearance of the original lesion, causing it to mimic a pyogenic granuloma.

• Is the patient pregnant? Oral pyogenic granulomas can develop during or just after the first trimester of pregnancy. Examine and properly identify these lesions of pregnancy to avoid misdiagnosis and overtreatment. These lesions are not generally harmful in pregnancy; however, induction of labor due to uncontrollable bleeding from a gingival lesion has been reported.[22, 23, 24, 25, 26, 27]

• Has the lesion recurred after surgical treatment? If so, was it excised and the skin closed primarily or was it treated with shave removal and electrodesiccation of the base? Pyogenic granulomas may recur. This is more likely when they are incompletely removed, but recurrence is also possible after apparently complete removal. Pyogenic granulomas are more likely to recur after shave removal and electrodesiccation of the base than after surgical excision.

• Has the patient taken oral retinoid therapy (isotretinoin [Accutane]) recently? Facial pyogenic granuloma–like lesions during isotretinoin therapy have been reported.

Pyogenic granulomas (PGs) appear as smooth firm nodules, with or without crusts, and they may have a bright or dusky red color. They are usually solitary, well circumscribed, dome shaped, 1-10 mm in diameter, and sessile or pedunculated.

In children, pyogenic granulomas are most commonly located on the head and neck (62.4%) and, in order of decreasing frequency, on the trunk (19.7%), upper extremity (12.9%), and lower extremity (5%). Most (88.2%) occur on the skin, and the rest involve mucous membranes of the oral cavity and conjunctivae.

In pregnant women, pyogenic granulomas are most often found on the gingival mucosa[24, 28] but they have been known to appear in nonoral areas such as the fingers and inguinal crease.

Pyogenic granulomas may occur within a port-wine stain; the presence of a vascular birthmark in the region of the pyogenic granuloma may be significant.

Amelanotic melanoma may closely mimic a pyogenic granuloma in appearance. Closely examine the skin immediately adjacent to the lesion for any pigmentary irregularity.

Complications for pyogenic granulomas (PGs) may include the following:

• Significant secondary infection (extremely uncommon)
• Recurrence at the original site
• Recurrence as multiple satellite lesions in the area immediately surrounding the original lesion
• Superficial scar formation

An oral pyogenic granulomas can develop during or just after the first trimester of pregnancy. Usually, an oral pyogenic granulomas is an early slow-growing mass that, upon excision, does not leave a large defect in the periodontium that requires surgical repair. Rarely, a rapidly growing large tumor may produce significant hemorrhage.

Lesions that do not respond appropriately to conservative treatment should undergo biopsy to confirm the diagnosis.

Proliferation of capillaries is present, with prominent endothelial cells embedded in edematous gelatinous stroma in a characteristic lobular configuration (see image below).

The epidermis is commonly eroded.

A dense infiltrate and granulation tissue with polymorphonuclear leukocytes may be present.

Hyperproliferation of the epidermis is usually present at the margins of the vascular growth, which results in a collarette of epidermis.[16, 29, 30]

Topical beta-blocker therapy remains a first-line treatment for pediatric pyogenic granuloma (PG) because of good efficacy and minimal adverse effects.[31, 32] Previous successful treatments have been topical timolol over 12-24 weeks;[31, 33] since then, case reports have suggested that the course may be shortened, with one case series showing resolution of ocular pyogenic granulomas over 21 days with no recurrence for at least 3 months[34] and another case report showing near-complete resolution at the scalp over 28 days.[35] Meanwhile, a prospective study of 22 children showed treatment with topical propranolol 1% ointment resulted in complete resolution in 13 children (59%) at a mean of 66 days[36] ; upon follow-up 2 years after resolution, there was no recurrence of the 13 pyogenic granulomas cured. While the exact mechanism is unknown, beta-blockers are thought to inhibit vascular endothelial growth factor (VEGF) and modulate the growth of vascular tumors, resulting in apoptosis over a long course of treatment.

Although not yet approved by the US Food and Drug Administration for pediatric pyogenic granulomas, possible upcoming treatments include ingenol mebutate 0.015% cream and topical imiquimod 5% cream. Ingenol mebutate is a cytoxic agent derived from the Euphorbia plant that has been successfully used in the treatment in actinic keratoses.[37] One case from 2017 reported complete resolution after 6 days of once-daily application; there was no evidence of recurrence at 5 months of follow-up.[38] Imiquimod is a synthetic imidazoquinoline heterocyclic amine that enhances, through cytokine induction, both the innate and acquired immune pathways, resulting in immunomodulating, antiviral, and antitumor effects.[39, 40, 41] Definitive data on its efficacy and safety on pediatric age groups are not established, but case reports describe its use in the treatment of molluscum contagiosum, anogenital warts, hemangiomas, and, more recently, pyogenic granuloma.[41] Treatment results were satisfactory with minimal scarring, and adverse effects were similar to those observed in adult patients.[42]

Nonmedical treatment of pyogenic granulomas (PGs) most commonly consists of shave removal and electrocautery or surgical excision with primary closure.[43] Removal of the lesion is indicated for bleeding due to trauma, discomfort, cosmetic distress, and diagnostic biopsy. The lesion may be completely removed during biopsy. In pediatric cases, a eutectic mixture of local anesthetics (EMLA) applied to the lesion and surrounding skin under an occlusive dressing for 1-2 hours prior to additional intralesional anesthesia may be of significant value.

For solitary lesions, a shave excision and electrocautery under local anesthesia is the treatment of choice. To provide an adequate cure rate, all vascular granulation tissue must be removed or cauterized.

For large or recurrent lesions, surgical excision with primary closure may be more effective. One study reported a 43.5% recurrence rate in 23 lesions treated by shave (intradermal) excision and cautery or cautery alone. Lesions treated by full-thickness skin excision and linear closure did not recur.

Various lasers serve as alternative options to surgery and have been shown to be effective in treating pyogenic granulomas. Therapy with a diode laser at wavelengths of 808-980 nm has been increasingly preferred, owing to providing a relatively bloodless surgical field while resulting in minimal swelling and scarring.[18, 44, 45] Other modalities include carbon dioxide and element-based lasers.[19, 20]

Cryotherapy or silver nitrate therapy may be effective for very small lesions and exhibited a low overall recurrence rate (1.62%). However, if nonsurgical management is undertaken, cauterization with silver nitrate should be the first-line treatment.[21, 39, 46]

Consider referral to a dermatologist if the diagnosis is in doubt or if the availability of adequate therapy is questionable.

Following removal of the pyogenic granuloma (PG), routine wound care is the only treatment required. Follow-up visits are required only if the lesion recurs. If the lesion recurs and histopathology confirms the diagnosis, the recurrent lesion may be treated with any of the modalities previously discussed, including simply repeating the initial therapy.