A 62-year-old female presented with a chief complaint of a soft tissue growth on her left big toe. She reported the lesion to be red, raised and bleeding with pressure. There was a small amount of drainage on the bandage she used to protect the foot in shoe gear.
The lesion began following a puncture wound with a stick while she was gardening the previous summer. The lesion was present for several months and then fell off when she was wearing closed toed shoes in the winter. The area of the soft tissue mass had nearly healed with the exception of a small area of discolored callus. Gradually, the lesion recurred over the last several months.
The patient’s past medical history included hypertension, hyperthyroidism, hyperlipidemia, impaired fasting glucose and sinusitis. Her medications included aspirin, vitamin D, estradiol, hydrochlorothiazide, levothyroxine, losartan (Cozaar, Merck) and simvastatin (Zocor, Merck). Her past surgical history included a hysterectomy. She denied tobacco or illicit drug use, and reported rare alcohol use.
The physical exam revealed a large pedunculated lesion extending off the plantar medial aspect of the left hallux. The lesion measured approximately 0.9 cm in diameter with a 0.3 cm stalk. It was red, bled easily with pressure and had surrounding maceration. I removed the lesion with full thickness surgical excision.
Key Questions To Consider
1. In what patient populations do these lesions occur?
2. What are the potential causes?
3. What are the differential diagnoses?
4. What are the recommended treatment modalities?
Answering The Key Diagnostic Questions
1. Pyogenic granulomas are common in children, adults in their 20s and pregnant females.
2. The most common causes of pyogenic granuloma include trauma and hormonal factors.
3. Differential diagnoses for pyogenic granuloma include angiokeratoma, bacillary angiomatosis, basal cell carcinoma and nodular melanoma.
4. The recommended treatment modalities for pyogenic granuloma are full thickness surgical excision or cauterization with silver nitrate.
What You Should Know About Pyogenic Granuloma
Pathological analysis revealed the presence of a pyogenic granuloma. Pyogenic granulomas are relatively common vascular lesions that arise on the skin and oral mucosa. Researchers have shown these lesions to result from irritation, trauma or hormonal factors.1,2 The lesions typically present as a solitary red, moist papule or nodule that bleeds easily. Pyogenic granulomas tend to present suddenly and grow rapidly over the course of a few weeks.
Pyogenic granulomas are also known as lobular capillary hemangioma, granulation tissue-type hemangioma, eruptive hemangioma, granuloma gravidarum and pregnancy tumors. Pyogenic granulomas are misnamed as they are neither infectious nor granulomatous. Authors have suggested that the most appropriate name for this neoplasm is lobular capillary hemangioma because the lesions consist of lobular clusters of capillaries in a dense stroma, accompanied by an inflammatory infiltrate.3
Pyogenic granulomas most commonly present as solitary papules or nodules with a shiny or moist red surface that bleeds easily with pressure. The lesions frequently develop rapidly over the course of a few weeks. The size of the lesions varies from several millimeters to a few centimeters. Some lesions may be pedunculated and quite large. The lesions may exhibit a small amount of drainage leading to maceration and crust formation of the surrounding normal soft tissues. Older lesions frequently develop an ulcerated surface or areas of necrosis. Resolving lesions present as soft, fibrous papules. The lesions occur at various sites including the head, neck, oral mucosa and areas prone to trauma including the digits and plantar foot.
Authors have reported several variant forms of pyogenic granuloma including disseminated pyogenic granuloma, pyogenic granuloma with satellitosis, intravenous pyogenic granuloma, subcutaneous pyogenic granuloma, eruptive pyogenic granuloma and medication-induced granuloma.4-9
Current Insights On Etiology, Pathophysiology And Epidemiology
A pyogenic granuloma commonly arises secondary to low-grade local irritation and/or traumatic injury. Hormonal factors play a role as well with pyogenic granuloma often presenting during pregnancy and less commonly with oral contraceptive use. The proliferative effect of estrogens theoretically contributes to the development of these lesions.10 In addition to trauma and hormonal factors, researchers have reported several other triggering factors for the development of pyogenic granuloma, including pulse dye laser, systemic and topical retinoids, antiretrovirals, chemotherapy, erythropoietin and anti-rheumatologic drug therapy.11-22
The specific pathophysiology for the development of pyogenic granuloma is unknown. Despite its name, pyogenic granulomas do not have an infectious etiology. It is poorly understood whether pyogenic granulomas are a reactive process or a tumor. Studies have suggested virus, arteriovenous malformations, abnormal production of angiogenic growth factors and cytogenic abnormalities to play a role in the development of pyogenic granuloma.23-27
Godfraind and colleagues showed a pyogenic granuloma to be more of a reactive process resulting from tissue injury followed by an impaired wound healing response during which vascular growth results from tyrosine-kinase receptors and the nitric oxide pathway.27 Other specific etiologic factors that play a role in the development of pyogenic granuloma include tumorigenesis secondary to over production of transcription factors pATF2 and STAT324, and angiogenesis with endothelial nitric oxide synthases, CD34 and CD105/endoglin expression.23,25
Pyogenic granulomas are common skin lesions accounting for 0.5 percent of all skin nodules in children and occurring in up to 5 percent of pregnancies.9,28 In children, there is a 3:2 male: female ratio.29 However, in adults, pyogenic granulomas are more common in females due to pregnancy lesions.29 Pyogenic granulomas occur most commonly in the second decade of life in adults and around 6 years of age in children.30
A Guide To Making A Differential Diagnosis
Differential diagnoses for pyogenic granuloma include angiokeratoma, bacillary angiomatosis, basal cell carcinoma and nodular melanoma.31
Angiokeratomas are benign cutaneous capillary lesions that present as small red to blue papules with hyperkeratosis. These lesions are typically smaller, slower growing and often multiple in comparison to larger, rapidly growing and solitary pyogenic granulomas.31
Bacillary angiomatosis is a vascular proliferative lesion associated with Bartonella infection. It occurs most commonly in immunocompromised individuals with a history of HIV infection, organ transplant, leukemia or chemotherapy.32 Bacillary angiomatosis has an appearance identical to pyogenic granuloma but tends to occur in greater numbers.
Basal cell carcinoma is a malignant skin neoplasm arising from the basal cell layer of the epidermis. Basal cell carcinoma is the most common form of skin cancer. It typically presents as a pearly papule with telangiectasia and the lesions may become ulcerated.31 Basal cell carcinoma grows at a slow rate in comparison to rapid growth of pyogenic granuloma.
Nodular melanoma presents as a rapidly enlarging red, black or skin colored lump that can have a smooth, rough or ulcerated surface.31 Nodular melanoma is the most aggressive type of melanoma with malignant cells that proliferate downward through the skin. It is the most important tumor to differentiate from pyogenic granuloma.
What You Should Know About Treating Pyogenic Granulomas
When it comes to pyogenic granulomas, there are several non-surgical treatment modalities, including topical agents, chemical cautery and intralesional injections.
Both topical imiquimod cream and alitretinoin gel (Panretin, Eisai) are reportedly successful topical treatments for pyogenic granuloma.33,34 Chemical cauterization with silver nitrate and topical phenol are treatment options although a recurrence rate of up to 43.5 percent has occurred with cautery treatment.29,35,36 In addition, injectable sclerosing agents, intralesional steroids, intralesional bleomycin and photodynamic therapy with 5-aminolevulinic acid intralesional injection are reportedly successful treatment modalities for pyogenic granuloma and recurrent lesions.37-40 Following a retrospective review of treatment modalities, Lee and colleagues recommended cauterization with silver nitrate as the initial non-surgical treatment for pyogenic granuloma.41
Several surgical options for the treatment of pyogenic granuloma exist. These treatments include shave, punch, curettage and scalpel excision. Researchers have also shown various laser modalities, as well as cryosurgery, to be successful treatment modalities for pyogenic granuloma.42,43 Full-thickness surgical excision has the lowest rate of recurrence at 2.94 percent and is the recommended treatment modality for smaller lesions in non-cosmetically sensitive areas.41
Pyogenic granulomas are commonly occurring, benign skin lesions that are more appropriately called lobular capillary hemangioma. The lesions frequently arise secondary to trauma or pregnancy. The recommended treatment for pyogenic granuloma includes cauterization with silver nitrate and full thickness surgical excision.
Dr. Hoffman is in private practice in Boulder, Colo.
1. Jafarzadeh H, Sanatkhani M, Mohtasham N. Oral pyogenic granuloma: a review. J Oral Sci. 2006;48(4): 167–75.
2. Freedberg IW, Eisen AZ, Wolff K, et al. Fitzpatrick's Dermatology in General Medicine, sixth edition. McGraw-Hill, New York, 2003.
3. Mills S, Cooper P, Fechner R. Lobular capillary hemangioma: the underlying lesion of pyogenic granuloma. Am J Surg Pathol. 1980;4(5):471-479.
4. Strohal R, Gillitzer R, Zonzits E, Stingl G. Localized vs. generalized pyogenic granuloma. A clinicopathologic study. Arch Dermatol. 1991;127(6):856-61.
5. Itin PH, Fluckiger R, Zbinden R, Frei R. Recurrent pyogenic granuloma with satellitosis--a localized variant of bacillary angiomatosis? Dermatology. 1994;189(4):409-12.
6. Saad RW, Sau P, Mulvaney MP, James WD. Intravenous pyogenic granuloma. Int J Dermatol. 1993;32(2):130-2.
7. Fortna RR, Junkins-Hopkins JM. A case of lobular capillary hemangioma (pyogenic granuloma), localized to the subcutaneous tissue, and a review of the literature. Am J Dermatopathol. 2007;29(4):408-11.
8. Shah M, Kingston TP, Cotterill JA. Eruptive pyogenic granulomas: a successfully treated patient and review of the literature. Br J Dermatol. 1995;133(5):795-6.
9. Pierson JC, Tam CC. Dermatologic manifestations of pyogenic granuloma (lobular capillary hemangioma). Medscape. Available at http://emedicine.medscape.com/article/1084701 . Published Feb. 27, 2014. Accessed April 2, 2014.
10. Hemady N. Growing plantar lesion following trauma. Am Fam Physician. 2006;74(7):1173-1174.
11. Cheah S, DeKoven J. Pyogenic granuloma complicating pulsed-dye laser therapy for cherry angioma. Australas J Dermatol. 2009;50(2):141-3.
12. Liu S, Yang C, Xu S, et al. Pyogenic granuloma arising as a complication of 595 nm tunable pulsed dye laser treatment of port-wine stains: report of four cases. Dermatol Surg. 2010;36(8):1341-3.
13. Campbell JP, Grekin RC, Ellis CN, et al. Retinoid therapy is associated with excess granulation tissue responses. J Am Acad Dermatol. 1983;9(5):708-13.
14. Badri T, Hawilo AM, Benmously R, et al. Acitretin-induced pyogenic granuloma. Acta Dermatovenerol Alp Panonica Adriat. 2011;20(4):217-218.
15. Teknetzis A, Ioannides D, Vakali G, et al. Pyogenic granulomas following topical application of tretinoin. J Eur Acad Dermatol Venereol. 2004;18(3):337-9.
16. Bouscarat F, Bouchard C, Bouhour D. Paronychia and pyogenic granuloma of the great toes in patients treated with indinavir. N Engl J Med. 1998;338(24):1776-7.
17. Wu PA, Balagula Y, Lacouture ME, Anadkat MJ. Prophylaxis and treatment of dermatologic adverse events from epidermal growth factor receptor inhibitors. Curr Opin Oncol. 2011;23(4):343-51.
18. Curr N, Saunders H, Murugasu A, et al. Multiple periungual pyogenic granulomas following systemic 5-fluorouracil. Australas J Dermatol. 2006;47(2):130-3.
19. Piguet V, Borradori L. Pyogenic granuloma-like lesions during capecitabine therapy. Br J Dermatol. 2002;147(6):1270-2.
20. Suarez-Amor O, Cabanillas M, Monteagudo B, et al. Disseminated pyogenic granuloma induced by erythropoietin? Actas Dermosifiliogr. 2009;100(5):439-40.
21. Higgins EM, Hughes JR, Snowden S, Pembroke AC. Cyclosporin-induced periungual granulation tissue. Br J Dermatol. 1995;132(5):829-30.
22. Wollina U. Multiple eruptive periungual pyogenic granulomas during anti-CD20 monoclonal antibody therapy for rheumatoid arthritis. J Dermatol Case Rep. 2010;4(3):44-6.
23. Vasconcelos MG, Alves PM, Vasconcelos RG, et al. Expression of CD34 and CD105 as markers for angiogenesis in oral vascular malformations and pyogenic granulomas. Eur Arch Otorhinolaryngol. 2011;268(8):1213-7.
24. Chen SY, Takeuchi S, Urabe K, et al. Overexpression of phosphorylated-ATF2 and STAT3 in cutaneous angiosarcoma and pyogenic granuloma. J Cutan Pathol. 2008;35(8):722-30.
25. Vassilopoulos SI, Tosios KI, Panis VG, Vrotsos JA. Endothelial cells of oral pyogenic granulomas express eNOS and CD105/endoglin: an immunohistochemical study. J Oral Pathol Med. 2011;40(4):345-51.
26. Isaza-Guzmán DM, Teller-Carrero CB, Laberry-Bermúdez MP, et al. Assessment of clinicopathological characteristics and immunoexpression of COX-2 and IL-10 in oral pyogenic granuloma. Arch Oral Biol. 2012;57(5):503-12.
27. Godfraind C, Calicchio ML, Kozakewich H. Pyogenic granuloma, an impaired wound healing process, linked to vascular growth driven by FLT4 and the nitric oxide pathway. Mod Pathol. 2013;26(2):247-55.
28. Sills ES, Zegarelli DJ, Hoschander MM, Strider WE. Clinical diagnosis and management of hormonally responsive oral pregnancy tumor (pyogenic granuloma). J Reprod Med. 1996;41(7):467-70.
29. Patrice SJ, Wiss K, Mulliken JB. Pyogenic granuloma (lobular capillary hemangioma): a clinicopathologic study of 178 cases. Pediatr Dermatol. 1991;8(4):267-76.
30. Harris MN, Desai R, Chuang TY, et al. Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions. J Am Acad Dermatol. 2000;42(6):1012-6.
31. Fitzpatrick TB. Color Atlas and Synopsis of Clinical Dermatology: Common and Serious Diseases, fifth edition. McGraw-Hill, New York, 2005, pp. 184–5.
32. Moulin C, Kanitakis J, Ranchin B, et al. Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review. Transpl Infect Dis. 2012;14(4):403-9.
33. Tritton SM, Smith S, Wong LC, et al. Pyogenic granuloma in ten children treated with topical imiquimod. Pediatr Dermatol. 2009;26(3):269-72.
34. Maloney DM, Schmidt JD, Duvic M. Alitretinoin gel to treat pyogenic granuloma. J Am Acad Dermatol. 2002;47(6):969-70.
35. Quitkin HM, Rosenwasser MP, Strauch RJ. The efficacy of silver nitrate cauterization for pyogenic granuloma of the hand. J Hand Surg Am. 2003;28(3):435-8.
36. Losa Iglesias ME, Becerro de Bengoa Vallejo R. Topical phenol as a conservative treatment for periungual pyogenic granuloma. Dermatol Surg. 2010;36(5):675-8.
37. Carvalho RA, Neto V. Letter: Polidocanol sclerotherapy for the treatment of pyogenic granuloma. Dermatol Surg. 2010;36 Suppl 2:1068-70.
38. Parisi E, Glick PH, Glick M. Recurrent intraoral pyogenic granuloma with satellitosis treated with corticosteroids. Oral Dis. 2006;12(1):70-2.
39. Daya M. Complete resolution of a recurrent giant pyogenic granuloma on the palm of the hand following single dose of intralesional bleomycin injection. J Plast Reconstr Aesthet Surg. 2010;63(3):e331-3.
40. Lee DJ, Kim EH, Jang YH, Kim YC. Photodynamic therapy with 5-aminolevulinic acid intralesional injection for pyogenic granuloma. Arch Dermatol. 2012;148(1):126-8.
41. Lee J, Sinno H, Tahiri Y, Gilardino MS. Treatment options for cutaneous pyogenic granulomas: a review. J Plast Reconstr Aesthet Surg. 2011;64(9):1216-20.
42. Mirshams M, Daneshpazhooh M, Mirshekari A, et al. Cryotherapy in the treatment of pyogenic granuloma. J Eur Acad Dermatol Venereol. 2006;20(7):788-90.
43. Yang C, Liu S. Treatment of giant pyogenic granuloma with the Nd/YAG holmium laser: a case report. J Cosmet Laser Ther. 2013;15(4):225-7.