Are You Confident of the Diagnosis?
What you should be alert for in the history
Pyogenic granuloma (PG; also referred to as lobular capillary hemangioma) usually presents as a red papule or nodule (<1 cm) with a propensity to bleed in children and young adults. Patients may recall precedent trauma. The lesion commonly goes through a rapid growth phase for a few weeks before stabilizing in size. It usually persists for months unless treated, and recurrence after treatment is possible.
Characteristic findings on physical examination
The most common location is the head and neck (especially the oral mucosa, cutaneous cheek and lip) (Figure 1), followed by the upper extremities (especially the finger), trunk and lower extremities. When a pyogenic granuloma appears on the oral mucosa of a pregnant woman, the lesion is called granuloma gravidarum. Other presentations include those within preexisting vascular lesions (such as nevus flammeus, spider angioma and hemangioma), intravascular lesions, and subcutaneous lesions. Rarely multiple pyogenic granulomas may occur.
On physical examination, a PG looks like an exophytic, friable papule (Figure 2). Ulceration or crust may be present, as the lesion bleeds easily.
Expected results of diagnostic studies
A skin biopsy is both diagnostic and therapeutic. Histopathologically, the term pyogenic granuloma is a misnomer as the lesion is neither pus-filled nor granulomatous. Rather, the synonym lobular capillary hemangioma accurately describes the histopathology. Biopsy reveals lobules of capillary proliferation in edematous stroma, similar to granulation tissue, separated by connective tissue septae. The lesion is often well-circumscribed with a peripheral epithelial collarette (Figure 3). If the lesion is ulcerated, the collarette is lost and inflammation may be present in the deeper dermis.
The differential diagnosis of PG includes the following papules or plaques: (1) hemangioma (histopathology lacks lobularity formed by fibrous bands); (2) venous lake (clinically more dark blue or black); (3) glomus tumor (clinically more blue and painful); (4) angiosarcoma or other neoplasms such as melanoma, especially those that are amelanotic or irritated, squamous cell carcinoma, or basal cell carcinoma (all of which show cell atypia on biopsy); or (5) verruca vulgaris or wart (clinically more verrucoid, biopsy with koilocytes).
If the patient is immunocompromised, (6) Kaposi sarcoma is an important consideration (histopathology shows spindle cells) as is (7) bacillary angiomatosis (biopsy positive for Bartonella bacilli with Warthin-Starry or Giemsa stains or PCR testing). Distinction in any patient from (8) Orf or milker’s nodule is helpful (history of exposure to farm animals, biopsy with viral inclusions due to the Parapoxvirus). Finally, if the lesion is mucosal, one must consider a (9) peripheral giant cell granuloma (clinically more bluish-purple than bright red).
Who is at Risk for Developing this Disease?
PG is a common, benign, vascular proliferation, thought to account for 0.5% of all pediatric cutaneous nodules. In children and young adults, males are slightly more affected than females. For mucosal lesions, however, women outnumber men as much as 2:1, since mucosal lesions are most often seen in pregnant women.
What is the Cause of the Disease?
PG may be associated with antecedent trauma, and as such the lesion has been thought of as a reactive vascular proliferation mediated by angiogenic growth factors. These include vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
Along these lines, PGs may occur as intravascular lesions or within preexisting vacular malformations (such as nevus flammeus, spider angioma and hemangioma). Pregnancy and oral contraceptives are implicated in mucosal PGs because of the angiogenic effects of estrogens. Other medications like retinoids (both oral and topical) and antitretroviral therapy (especially indinavir) are known to cause PGs, presumably because of their angiogenic properties. Epidermal growth factor receptor (EGFR) inhibitors are also associated with the development of PGs by unknown mechanisms. Finally, Bartonella has been postulated as a cause, as this bacteria produces vascular lesions.
As PGs can be a vascular response to trauma, friction can produce multiple lesions, especially in mucosal and periungual sites. For example, patients with peripheral nerve injuries have been documented to have multiple periungual PGs secondary to greater than normal mechanical trauma.
Systemic Implications and Complications
There are no systemic complications related to PG per se. Multiple PGs are rare but may be seen in the context of inflammatory systemic diseases, such as cutaneous sarcoidosis, psoriasis, and seronegative spondyloarthritis. Such presentations may be related to a predisposition to form granulation tissue in chronic inflammatory diseases. Therefore, a patient presenting with multiple PGs should have a thorough investigation of the skin and joints in order to look into these possible underlying systemic disorders, if not already known.
Treatment options are summarized in Table I.
|Medical Treatment||Surgical Procedures||Physical Modalities|
|Topical high-potency corticosteroidsTopical imiquimod||Full-thickness skin excision with linear closureShave excision with or without cauteryCurettage with or without cauteryCautery alone (chemical or thermal)||585- or 595-nm pulsed-dye laser (PDL)Cryotherapy with liquid nitrogen1,064-nm neodymium-doped yttrium aluminim garnet (Nd:YAG) laser10,600-nm carbon dioxide laser|
|Sclerotherapy with monoethanolamine oleate, sodium tetradecyl sulfate, or ethanol|
Optimal Therapeutic Approach for this Disease
Diagnose and treat any underlying disorders contributing to the development of PGs. Stop or reduce offending drugs, such as oral contraceptives, retinoids, indinavir, or EGFR inhibitors. Treat any underlying disorders, such as cutaneous sarcoidosis, psoriasis or seronegative spondyloarthritis, which may predispose patients to producing granulation tissue. Limit trauma and mechanical friction, and encourage careful oral hygiene to prevent mucosal PGs, especially during pregnancy.
Every effort should be made to preserve histopathology in order to rule out malignancy, especially if the diagnosis is questionable. Ideally, full-thickness skin excision with linear closure is the preferred treatment, as it allows for histopathological examination and offers the lowest recurrence rate (reported as 0-3.7%). However, simpler surgical methods are more practical. If location and cosmetic outcome allow, shave excision with cautery of the base is a popular treatment with a recurence rate of 0-5%. Shave excision or cautery alone have a higher recurrence rate.
When the clinician is confident of the diagnosis, the 585- or 595-nm pulsed-dye laser (PDL) is a useful alternative to surgery. PDL is best suited for small PGs (<5 mm). A good starting point for settings (on V-beam) are fluences of of 7-10 J/cm2, pulse duration of 1.5 ms, and spot-size of 7 mm with dynamic cooling. Settings can then be adjusted according to clinical efficacy, as usually two, or as many as five, PDL treatments are required for clearance. Larger (>5 mm) lesions do not respond as well because of the laser’s limited penetration depth. However, advantages include good cosmetic results and acceptability in children.
Crythotherapy offers another alternative to surgery, and is especially good for PGs on a smooth mucosal surface. However, cryotherapy often requires multiple treatments. In a study of 89 patients with cutaneous PGs, patients treated with cryotherapy required one to three sessions for resolution, while those treated with curettage and electrodessication only required one to two sessions.
Large lesions (>5 mm) can be accommodated by the 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser because of it greater depth of penetration compared to PDL. Usually a few treatments spaced 2-3 weeks apart are required, and the risk of atrophic scarring is greater than that for PDL. One study used the Nd:YAG laser (Gentle-YAG) with settings of 3- to 1.5-mm spot size at 200-360 J/cm2 , a pulse width of 40 ms, and cryogen spray cooling.
Like the Nd:YAG laser, the carbon dioxide laser has a greater depth of penetration compared to PDL and can be used for PGs >5 mm. The carbon dioxide laser ablates lesions by destroying cells through rapid heating and vaporization of intracellular fluid, thus producing greater scarring compared to the Nd:YAG laser. Both pulsed (<1 millisecond) and continuous-wave (CW) modes have been used, but it seems the CW mode may be preferred to decrease the risk of scarring.
In a study of 100 patients, 98 patients cleared after only one treatment with a 10,600-nm carbon dioxide laser that was first used in continuous mode (power, 15W) until the lesion flattened, and then switched to pulsed mode (pulse length, 0.6-0.9 milliseconds; energy fluence, 500 mJ/pulse).
For PGs of the nail unit, there is evidence that alternating topical high-potency corticosteroids (clobetasol propionate ointment) with topical antibiotics (mupirocin ointment) under occlusion clears lesions and prevents secondary infection. For patients with cutaneous PGs who cannot tolerate treatment with surgery, physical modalities, or injections, topical imiquimod has been successful. In a study of 10 children, imiquimod 5% cream applied three times a week and increasing to daily as tolerated for duration of up to 2 months cleared all but one patient.
For giant or multiple PGs, systemic corticosteroids may be helpful. For example, a patient with an underlying inflammatory disease and multiple periungual PGs cleared with intramuscular triamcinolone acetonide.
Curettage with or without cautery has a recurrence rate as high as 10% and causes scarring. However, a study of 89 patients showed that curettage and electrodessication cleared lesions in one to two sessions, whereas cryotherapy took one to three sessions. Cautery alone (either chemical, as with silver nitrate, or thermal) has a higher recurrence rate compared to other methods and causes scarring.
Sclerotherapy with monoethanolamine oleate, sodium tetradecyl sulfate, or ethanol has been successful in a limited number of cases. In a study of nine patients with mucosal and cutaneous PGs as large as 10 x 15 mm, monoethanolamine oleate was diluted 2:1 with water and injected directly into PGs (without local anesthesia) until the medication leaked out from the lesion (dose ranged from 0.1 mL to 2 mL). All lesions cleared within 2 weeks after only one injection.
For complex or recurrent lesions, a combination of surgery, cryotherapy, laser therapy, medical therapy, sclerotherapy, or a combination of the above, sometimes in multiple installments, may be helpful. For example, one synergistic technique is to shave the lesion, compress the base with a glass slide, and photocoagulate the base with a laser. Other studies have shown laser therapy followed by sclerotherapy to be effective.
Explain to patients that a PG is a benign vascular proliferation. If the diagnosis is questionable, every effort should be made for surgical removal with histopathological examination in order to rule out malignancy, especially amelanotic melanoma. Given that the lesion is prone to bleeding, most patients seek treatment and are happy to cooperate.
Inform patients of the risk of recurrence with any treatment modality, as none is perfect and PGs are notorious for recurring. All efforts should be made to encourage surgical removal, as this option allows for histopathological examination and offers the lowest recurrence rate. However, surgical modalities must be balanced with patient tolerance of the procedure and anesthetic outcomes. Lasers, such as PDL and Nd:YAG lasers, minimize scarring and are usually tolerated by children.
For recurrent, complex or multiple PGs, nonsurgical therapies are less invasive and offer good cosmetic results, but tell patients that these options have a higher rate of recurrence and often require multiple treatments.
Unusual Clinical Scenarios to Consider in Patient Management
When treating pregnant women who are most prone to PGs of the oral mucosa, surgical and periodontal treatment should be performed during the second trimester or postpartum period. There is debate as to which period is optimal, so ask patients about their preferences when timing therapy. Encourage all pregnant women to perform careful oral hygiene for prevention of PGs.
What is the Evidence?
Giblin, AV, Clover, AJP, Athanassopoulos, A, Budny, PG. “Pyogenic granuloma – the quest for optimum treatment: audit of treatment of 408 cases”. J Plast, Reconstr Surg. vol. 60. 2007. pp. 1030-5. (An excellent retrospective study of 408 cases with emphasis on treatment. The authors recommend surgical excision with linear closure because it allows for histopathological analysis and has the lowest recurrence rate.)
Pagliai, KA, Cohen, BA. “Pyogenic granuloma in children”. Ped Dermatol. vol. 21. 2004. pp. 10-13. (A retrospective study of 128 cases of pediatric PG with a discussion of different treatment modalities. The most common treatment was shave excision and electrocautery with no reported recurrences. The authors recommend this method for uncomplicated pyogenic granulomas.)
Jafarzadeh, H, Sanatkhani, M, Mohtasham, N. “Oral pyogenic granuloma: a review”. J Oral Sci. vol. 48. 2006. pp. 167-75. (A thorough review of oral PGs with discussion of pathophysiology, correlation with pregnancy, differential diagnosis and treatment.)
Piraccini, BM, Bellavista, S, Misciali, C, Tosti, A, de Berker, D, Richert, B. “Periungual and subungual pyogenic granuloma”. Br J Dermatol. vol. 163. 2010. pp. 941-53. (A retrospective study of 58 cases of nail PGs, with an especially good discussion of etiologies and treatments.)
Sud, AR, Tan, ST. “Pyogenic granuloma – treatment by shave-excision and/or pulsed-dye laser”. J Plast Reconstr Surg. vol. 63. 2010. pp. 1364-8. (This study of 49 patients (aged 6 weeks to 87 years) evaluates the use of pulsed-dye laser (PDL) in 51 cutaneous and lip lesions. The authors recommend PDL for lesions < 5 mm, which requires an average of 1.8 PDL treatments, and shave-excision with immediate PDL to the base for larger lesions.)
Galeckas, KJ, Uebelhoer, NS. “Successful treatment of pyogenic granuloma using a 1,064-nm laser followed by glycerin sclerotherapy”. Dermatol Surg. vol. 35. 2009. pp. 530-4. (This case report details the treatment of an adolescent with a pyogenic granuloma on the upper lip. The lesion was successfully treated with three treatments of 1,064-nm Nd:YAG, the first two of which were immediately followed by sclerotherapy with glycerin.)
Bédard, MS, Boulanger, J. “Treatment of lobular capillary hemangioma with the Nd:YAG laser: retrospective case series of 25 patients”. J Cut Med Surg. vol. 13. 2009. pp. 181-2. (A retrospective case series of 25 PG patients (ages 6 to 66 years) treated with the 1,064-nm Nd:YAG laser (fluence 100-130 J/cm 2, number of pulses 1-14). The mean number of treatments of 2.28 spaced 2-3 weeks apart, and 44% cleared with one session. No recurrences were seen after 2 months of follow-up.)
Raulin, C, Greve, B, Hammes, S. “The combined continuous-wave/pulsed carbon dioxide laser for treatment of pyogenic granuloma”. Arch Dermatol. vol. 138. 2002. pp. 33-7. (This prospective observational study of 100 patients (aged 6 months to 84 years) with mostly cutaneous lesions showed that 98 patients were treated with only one treatment of carbon dioxide laser. The 10,600-nm carbon dioxide laser was first used in continuous mode (power, 15W) and then in pulsed mode [pulse length, 0.6-0.9 milliseconds; energy fluence, 500 mJ/pulse].)
Ghodsi, SZ, Raziei, M, Taheri, A, Karami, M, Mansoori, P, Farnaghi, F. “Comparison of cryotherapy and curettage for the treatment of pyogenic granuloma: a randomized trial”. Br J Dermatol. vol. 154. 2006. pp. 671-5. (In this study of 89 patients (aged 11 to 85 years) with cutaneous PG randomized to receive treatment with cryotherapy with liquid nitrogen or curettage and electrodesiccation, resolution was obtained after one to three sessions of cryotherapy vs. one to two sessions in the curettage group.)
Tritton, SM, Smith, S, Wong, L, Zagarella, S, Fischer, G. “Pyogenic granuloma in ten children treated with topical imiquimod”. Ped Dermatol. vol. 26. 2009. pp. 269-72. (In this study of 10 pediatric patients with cutaneous PGs on the face, treatment with topical imiquimoid 5% cream resolved all but one lesion. Imiquimod use varied from daily to three times a week, for a duration of >1 to >17 weeks.)
Matsumoto, K, Nakanishi, H, Seike, T, Koizumi, Y, Mihara, K, Kubo, Y. “Treatment of pyogenic granuloma with a sclerosing agent”. Dermatol Surg. vol. 27. 2001. pp. 521-3. (This report of nine patients (aged 1 to 57 years) discusses the use of monoethanolamine oleate as a sclerosing agent for mucosal and cutaneous lesions as large as 10 x 15 mm. All patients cleared within 2 weeks after one treatment.)
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