Pyogenic granuloma (lobular capillary hemangioma)

INTRODUCTION — Pyogenic granuloma (PG) or lobular capillary hemangioma is a benign vascular tumor of the skin or mucous membranes characterized by rapid growth and friable surface [1]. PG occurs at any age, although it is seen more often in children and young adults. Surgical treatment is usually required because PG rarely resolves spontaneously and often bleeds repeatedly and profusely.

This topic will discuss the pathogenesis, clinical manifestations, diagnosis, and treatment of PG. Other benign and malignant vascular tumors are discussed separately. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)" and "Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment" and "AIDS-related Kaposi sarcoma: Staging and treatment".)

EPIDEMIOLOGY — Pyogenic granuloma (PG) occurs in patients of all ages, with a peak incidence in the second and third decades of life [2,3]. In children, the average age at diagnosis is 6 to 10 years, and there is a predilection for males [3-5]. Mucosal PG is more common in adult women than in men and is relatively common in children [6,7]. In a review of clinical and pathologic studies including nearly 86,000 pediatric patients seen at oral disease clinics and over 40,000 oral mucosal biopsies, PG was diagnosed in approximately 5 percent of cases [8]. Approximately 2 to 3 percent of pregnant women develop an intraoral PG in the first five months of pregnancy [9,10]. (See "Maternal adaptations to pregnancy: Skin and related structures", section on 'Vascular tumors'.)

PATHOGENESIS — Although the name suggests an infectious etiology, the cause of pyogenic granuloma (PG) is unknown. Most theories on pathogenesis revolve around PG as a hyperplastic, neovascular response to an angiogenic stimulus with imbalance of promoters and inhibitors [3,11]. An analysis of 11 PGs revealed embryonic stem cell markers in the endothelial cells and a more differentiated pattern in the interstitial cells, suggesting de novo vasculogenesis from the primitive stem cells [12].

Angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and decorin, transcription factors (pATF2 and pSTAT3), and mitogen-activated protein kinase (MAPK) signal transduction pathway proteins are overexpressed in PGs, but their exact role is undetermined [11,13,14]. A whole exome sequencing study of 40 PG lesions found HRAS somatic mutations in four tumors, supporting a role for the RAS-MAPK pathway in the development of PG [15]. MAPK/ERK pathway activation has been demonstrated in oral PGs [16].

Trauma has been suggested as a trigger, although only 7 to 23 percent of patients with PG report a previous injury at the site [4,5]. In a series of patients with periungual or subungual PG, local injury (eg, acute mechanical trauma, onycholysis, or chronic nail manipulation) was reported in 58 percent of cases [17]. Patients who have undergone hematopoietic cell transplant have been reported to develop mucosal PG thought to be related to the trauma of oral graft-versus-host disease or medications taken post-transplant [18].

PG may also be drug-induced [11,17,19-29]. In one study, approximately 30 percent of cases of periungual or subungual PG were related to a systemic medication [17]. Offending medications include:

●Systemic retinoids [30] (see "Oral isotretinoin therapy for acne vulgaris", section on 'Adverse effects')

●Epidermal growth factor receptor (EGFR) and tyrosine kinase inhibitors (eg, cetuximab, imatinib [29,31])

●BRAF inhibitors (eg, vemurafenib, encorafenib) [29,32]

●VEGF receptor antibody (ramucirumab) [33]

●Capecitabine and etoposide

●Topical fluorouracil

●Cyclosporine, tacrolimus

●Docetaxel

●Granulocyte colony-stimulating factor

●Human immunodeficiency virus (HIV) protease inhibitors

(See "Cutaneous adverse effects of conventional chemotherapy agents" and "Cutaneous adverse events of molecularly targeted therapy and other biologic agents used for cancer therapy".)

PG may occur within a capillary vascular malformation (ie, port wine stain [PWS] (picture 1A-B)) spontaneously or following laser treatment [34-37]. This supports a hypothesis that PG arises from microscopic arteriovenous anastomoses, which may be found in capillary malformations and in common locations for PG, such as acral sites and oronasal mucosa [34].

In one study of 10 PGs arisen in a PWS, eight were found to harbor a BRAF c.1799T>A mutation and one a NRAS mutation. In addition, a GNAQ c.548G>A mutation was identified in all but one PG and in the respective underlying PWS [38]. These findings indicate that PGs originate from endothelial cells of the PWS and that BRAF mutations may act as a second hit on the GNAQ mutation-activated MAPK signaling pathway in endothelial cells, leading to tumor growth. The report of PG arising in the setting of selective BRAF inhibitor treatment supports this theory [18]. (See "Capillary malformations (port wine stains) and associated syndromes", section on 'Pathogenesis'.)

CLINICAL PRESENTATION

General features — Pyogenic granuloma (PG) starts as a small, red papule that grows rapidly over weeks to months and then stabilizes (picture 2A). Most lesions are solitary, but there are reports of multiple PGs arising in a disseminated fashion. In adults, PG occurs most often on the trunk or extremities, whereas in children, lesions are more commonly seen on the head and neck [2-5].

The size rarely exceeds one centimeter. The lesion may be pedunculated or sessile, and its base is often surrounded by a characteristic collarette of acanthotic epidermis (picture 3A-E).

Most PGs arise on normal-appearing skin or mucosal surfaces. However, PG may also arise in a capillary vascular malformation (ie, port wine stain, nevus simplex (picture 4)) or arteriovenous malformation, sometimes following laser treatment or cryotherapy [34,35,39-42]. Periungual PGs may also develop as a complication of drug-induced paronychia (picture 5).

The skin is more commonly involved than the mucosa. In a review of 325 cases of PG, 86 percent were located on the skin [2].

Clinical variants

Mucosal pyogenic granuloma — Mucosal PGs usually occur in the oral cavity. The predominant sites are the lip and gingival mucosa (picture 2A-B) [1,6]. Rarely, PG develops in the gastrointestinal tract; patients may be asymptomatic or present with overt bleeding, anemia, or dysphagia [43-46].

Intraoral PG presents as a red or purplish, smooth papule or nodule, ranging in size from several millimeters to approximately 2.5 cm [47]. Lesions can be solitary or multiple, sessile or pedunculated, and bleed easily after minor trauma.

Disseminated/multiple pyogenic granuloma — Disseminated PGs may occur in otherwise healthy individuals or in association with drug eruptions, burn injury, or treatment with anti-CD20 monoclonal antibodies or granulocyte colony-stimulating factor [27,48-51]. Multiple grouped PGs may develop in infants and young children over a pre-existing vascular malformation, particularly capillary or arteriovenous malformations [52].

Uncommonly, multiple PGs develop as satellite lesions spontaneously or following treatment of a solitary PG (recurrent PG with satellitosis) (picture 6) [53-56]. This phenomenon usually occurs in children and may resolve spontaneously in 6 to 12 months [55].

Congenital pyogenic granuloma — Congenital PGs are extremely rare and difficult to discern from infantile hemangiomas without histopathologic examination and glucose transporter 1 (GLUT1) staining [57,58]. Congenital PGs may be solitary or disseminated and may affect the skin and the mucosal surfaces [59,60]. A severe form of congenital, disseminated PG involving the skin and internal organs (eg, central nervous system, liver, spleen, muscles, bone, bowel, lung, kidney) has been described in a few infants [61]. (See 'Pathology' below.)

Intravascular pyogenic granuloma — Intravascular pyogenic granuloma (IVPG), also known as intravascular lobular capillary hemangioma, is a rare variant of PG that occurs within the lumen of an existing vessel [62,63]. Most cases occur in the lumen of veins of various calibers [64]; intra-arterial PG is exceedingly rare [65,66].

Clinically, IVPGs present as subcutaneous nodules most frequently located on the head, neck, or upper extremities, but they may occur in any part of the body. IVPGs are often asymptomatic and not associated with a history of trauma or surgery in the affected area. An IVPG may be slow growing or stable in size [63]. The histopathology is similar to that of cutaneous PG.

The diagnosis of IVPG may be suggested by ultrasound demonstrating a well-defined, hypoechoic mass adherent to the wall of the vein [67]. Anechoic, tubular-like, vascular structures within the nodule have been described. Color doppler flow imaging reveals hypervascularity. Ultimately, histopathology confirms the diagnosis [67].

CLINICAL COURSE AND COMPLICATIONS — Pyogenic granuloma (PG) bleeds profusely after minor trauma and may become ulcerated. There is little information about the natural history of untreated PG. Most lesions are treated because of frequent bleeding, ulceration, or cosmetic appearance. Bleeding is difficult to control and often recurrent. In clinical experience, PGs generally do not spontaneously involute, but there are exceptions:

●Spontaneous regression of PG over the course of 6 to 18 months has been reported in a few patients [4].

●Drug-induced PG may regress upon discontinuation of the offending medication [17].

●Oral PGs occurring in pregnant women often regress after childbirth [68].

●Satellite PGs that develop spontaneously or after treatment of a solitary PG (picture 6) may also resolve without treatment after 6 to 12 months [55].

●In disseminated PG, the majority of lesions eventually resolve spontaneously [58,69].

PATHOLOGY — Low power examination of pyogenic granuloma (PG) shows a polypoid lesion with a lobular arrangement of capillaries at the base (picture 7A). The epidermis overlying the pedunculated mass may be flattened, atrophic, and, often, ulcerated. At the base of the lesion, the epidermis is acanthotic with inward growth representing the "epithelial collarette" [5]. The pedunculated morphology and epithelial collarette are seen in most PG occurring on the skin but only in 30 percent of mucosal PG, mainly in those involving the oral mucosa [1].

The vessel lumina vary in size. Superficial stromal edema, capillary dilatation, inflammation, and granulation tissue may be seen [1].

On higher power, plump endothelial cells line the capillaries (picture 7B). They are surrounded by a mixed cell population of fibroblasts, mast cells, lymphocytes, plasma cells, and polymorphonuclear leukocytes [5].

Immunohistochemistry staining is negative for glucose transporter 1 (GLUT1) but positive for Wilms tumor I gene expression, factor VIII antigen, CD31, CD34, and Ulex europaeus agglutinin lectin [70-73]. GLUT1 stain is helpful in differentiating PG from infantile hemangiomas, which usually stain positively.

DIAGNOSIS — The diagnosis of pyogenic granuloma (PG) is usually straightforward, based upon the clinical history of an erythematous, dome-shaped papule that bleeds easily and has developed over a few days to weeks (picture 3C, 3E). Dermoscopic examination reveals a pink, homogenous papule with a white collarette of scale; white, intersecting lines representing the fibrous septa seen on histopathology may also be seen (picture 8) [74].

Histopathologic confirmation is helpful in excluding disorders that may mimic PG. Excisional biopsy provides the optimal pathologic specimen for excluding malignant tumors. However, any specimens obtained by other treatment modalities, such as shave excision or curettage, should also be sent for histopathologic examination. (See 'Pathology' above and 'Management' below.)

DIFFERENTIAL DIAGNOSIS — The disorders that should be differentiated from pyogenic granuloma (PG) include [4,75]:

●Infantile hemangioma – Infantile hemangiomas present as bright red papules, nodules, or plaques that appear in early infancy and grow rapidly (picture 9). Unlike PG, bleeding is uncommon and is usually well controlled with firm pressure. Infantile hemangiomas involute, whereas PG do not regress spontaneously [57]. Histologic examination during the proliferation stage demonstrates superficial proliferating angioblastic endothelial cells with few capillary lumina. In contrast to PG, immunohistochemistry staining is positive for glucose transporter 1 (GLUT1); however, in most cases, the diagnosis of infantile hemangioma is made without biopsy. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)

●Spindle and epithelial cell nevi (Spitz nevi) – Spitz nevi present as brown or red, dome-shaped, firm papules with an intact surface (picture 10). Typically, there is not a history of bleeding. On dermoscopic examination, dotted vessels and white lines may be visible. Histologically, Spitz nevus is a symmetrical and well-defined compound nevus consisting of spindle-shaped or epithelioid melanocytes. (See "Spitz nevus and atypical Spitz tumors".)

●Glomus tumor – Glomus tumor is a rare, benign neoplasm composed of cells resembling smooth cells of the normal glomus body [76]. Glomus tumor is usually located in skin areas rich in glomus bodies (eg, the subungual regions of digits or the deep dermis of the palm, wrist, forearm, and foot) and presents as a red-purple, vascular papule or nodule associated with paroxysmal pain, cold sensitivity, and tenderness (picture 11). Glomus tumor does not bleed or ulcerate. Histologic examination demonstrates a solid mass of glomus cells, vessels, and smooth muscle cells. (See "Overview of benign lesions of the skin", section on 'Glomus tumor'.)

●Common wart – Common warts present as solitary or multiple, firm, hyperkeratotic papules that may occasionally be necrotic at the surface or bleed (picture 12A-B). Clinical or dermoscopic examination after removing the hyperkeratotic layer reveals thrombosed vessels ("black dots"). (See "Cutaneous warts (common, plantar, and flat warts)".)

●Amelanotic melanoma – Amelanotic melanoma is often misdiagnosed as PG. On dermoscopic examination, amelanotic melanoma may have subtle, melanocytic structures or irregular, vascular patterns (picture 13). Histologic examination is necessary for a correct diagnosis. (See "Melanoma: Clinical features and diagnosis", section on 'Amelanotic melanoma'.)

●Squamous cell carcinoma – Squamous cell carcinoma (SCC) usually presents as a slow-growing lesion with a hyperkeratotic surface (picture 14); keratoacanthoma-type SCC develops quickly with a central keratotic core but is not friable (picture 15). Histologic examination is needed to confirm the diagnosis. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis".)

●Basal cell carcinoma – Nodular basal cell carcinoma presents as a pearly, slow-growing papule, sometimes with surface crust or ulceration (picture 16). On dermoscopy, blue globules; large, blue-gray, ovoid nests; arborizing telangiectasias; leaf-like areas; or spoke-wheel structures may be seen (picture 17) [74]. Histology is necessary to confirm the diagnosis. (See "Epidemiology, pathogenesis, clinical features, and diagnosis of basal cell carcinoma", section on 'Clinical presentation'.)

●Kaposi sarcoma – Kaposi sarcoma presents as slow-growing, violaceous papules and plaques, usually multiple in number. Elevated or polypoid lesions are rare and may mimic PG, although profuse bleeding unusual (picture 18) [77]. Biopsy is required for definitive diagnosis of Kaposi sarcoma. (See "AIDS-related Kaposi sarcoma: Staging and treatment" and "Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment".)

●Bacillary angiomatosis – Bacillary angiomatosis is caused by infection with Bartonella henselae or Bartonella quintana and usually occurs in HIV-infected or immunocompromised patients. Multiple vascular papules and nodules similar to PG occur (picture 19A-B). Histologic examination shows lobular, vascular proliferations of vessels lined by plump endothelial cells with clusters of neutrophils and lymphocytes (picture 20). Warthin-Starry stain demonstrates clumps of small, pleomorphic bacilli (picture 21). (See "Bartonella infections in people with HIV", section on 'Bacillary angiomatosis'.)

●Angiolymphoid hyperplasia with eosinophilia – Angiolymphoid hyperplasia with eosinophilia is a rare disorder presenting as solitary or multiple, erythematous or violaceous papules or nodules in the head and neck region (picture 22). Histologically, a prominent vascular proliferation with large, epithelioid endothelial cells is associated with an infiltrate of lymphocytes and eosinophils. (See "Angiolymphoid hyperplasia with eosinophilia and Kimura disease".)

MANAGEMENT

General considerations — Although spontaneous regression may occur in some patients, treatment is usually required for pyogenic granuloma (PG) because of frequent ulceration and bleeding. There are few randomized trials comparing treatments for PG, and there is no consensus regarding the optimal approach. Many treatment modalities have been described in retrospective series and case reports. These include surgical treatments (full-thickness excision, shave excision, curettage, laser therapy, cryotherapy), topical and intralesional therapies, and combinations of surgical and nonsurgical therapies.

In a review of 1162 PGs treated with 19 different modalities, surgical treatments, including full-thickness excision, shave excision, or curettage, were used in 65 percent of cases [78]. Destructive treatments included cryotherapy, laser therapy, and intralesional or topical agents. The recurrence rates for different treatment modalities for PG are summarized in the table (table 1).

Because malignant tumors can mimic PG, it is desirable that the technique(s) selected for removal of PG yield material for histopathologic analysis. Additional factors influencing the choice of treatment are the morphology, size, and location of the lesion; patient's age; and risk of recurrence and scarring. Provoking factors (eg, trauma, foreign body, or medication), if present, should be prevented, removed, or discontinued if feasible.

Lesions in noncosmetically sensitive areas

Surgical excision — For adults and children who can tolerate local anesthesia, we suggest surgical excision rather than destructive or topical treatments for most PG located in noncosmetically sensitive areas. Full-thickness surgical excision provides the optimal specimen for histologic confirmation of diagnosis and has the lowest rates of recurrence. Scarring is the main drawback of surgical treatment.

For nonpedunculated (sessile) PG, a narrow, elliptical excision of skin beneath the lesion to the subcutaneous fat layer followed by wound closure with sutures is appropriate to control bleeding and minimizes the risk of recurrence. Punch excision may be used for small PGs. (See "Fusiform/elliptical excision" and "Skin biopsy techniques", section on 'Punch biopsy'.)

Alternative surgical techniques for pedunculated PG include shave excision or curettage followed by laser photocoagulation or electrocautery of the base. This quicker procedure may also be considered for nonpedunculated lesions in younger children who cannot tolerate surgical excision. However, the risk of recurrence may be higher with these techniques. (See "Skin biopsy techniques", section on 'Shave biopsy' and "Minor dermatologic procedures", section on 'Curettage and electrodesiccation' and "Laser and light therapy for cutaneous vascular lesions".)

Tissue that is obtained through full-thickness excision, shaving, or curettage should be placed in formalin and sent for pathologic examination. For diagnostic purposes, full-thickness excision or shave excision provide the optimal specimen for histologic examination.

High-quality studies comparing surgical treatment with other treatment modalities for PG are lacking. Evidence supporting surgical excision is based on observational studies; a few small, randomized trials; and on clinical experience [1,5,78]:

●In a review of 753 PGs treated surgically, the recurrence rate for full-thickness excision and primary closure was 2.9 percent, whereas other surgical modalities, such as curettage and electrocautery or electrocautery alone, were associated with recurrence rates of 7 to 15 percent (table 1) [78]. A recurrence rate of 13 percent has been reported for intraoral PG treated by shave excision [3].

●In a series of 76 children aged 4 months to 17 years with PG mostly located on the head and neck, 58 (76 percent) were treated with surgical excision and electrocautery and 12 with either pulsed dye laser (PDL) or carbon dioxide (CO₂) laser [4]. None of the children treated with excisions experienced recurrence, whereas 6 of the 12 patients treated with laser therapy had recurrent or persistent lesions.

●In a small, randomized trial, 89 patients with clinically diagnosed PG were treated with curettage and electrodessication of the base or cryotherapy [79]. Among the 76 patients who completed the study, complete resolution after a single treatment was noted in 97 percent of patients in the curettage and electrodessication group versus 63 percent in the cryotherapy group. Scar and/or hypo- or hyperpigmentation occurred less frequently in the curettage group than in the cryotherapy group (31 versus 43 percent) [79]. These results should be interpreted with caution, however, because typical cryotherapy regimens usually involve more than one treatment [78,80].

Other treatments — A variety of treatments have been used for the treatment of PG in adults and children. These include electrocautery, laser therapy, cryotherapy, photodynamic therapy, and topical and intralesional therapies. We use cryotherapy or topical or intralesional therapies less often for PG, as these approaches are generally associated with a higher recurrence rate compared with surgical excision, often require repeated or prolonged treatments, and most importantly, do not provide specimens for histopathologic confirmation:

●Laser therapy – Laser therapy with pulsed dye laser (PDL), carbon dioxide (CO₂) laser, and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser have been used for treatment of PG in children and adults [4,81-85]. PDL and other vascular lasers do not allow for histologic examination and may leave hypo- or hyperpigmentation. (See "Laser and light therapy for cutaneous vascular lesions".)

With PDL, multiple treatment sessions are usually required because of the limited penetration of PDL in the dermis:

•In a series of 22 children with small PG (average size 4 mm) treated with PDL, 15 required two to six laser treatments [81]. Twenty patients responded to treatment and healed without scarring, and two patients underwent subsequent shave excision and electrocautery.

•In another series of 49 adult and pediatric patients with 51 lesions, an average of two (range: one to five) sessions were required for lesions <5 mm, and an average of three (range: one to six) sessions were needed for lesions 5 to 10 mm in size [83].

•In a retrospective review of 212 pediatric patients treated with PDL, 98 percent experienced complete resolution, and 4 percent changed treatment to CO₂ laser [86]. One session was successful in 66.8 percent of those treated with PDL, and 33.2 percent required two or three sessions. The mean size of PG in the study was 1.5 mm in height and 2.3 mm in diameter.

The CO₂ laser generally removes PG lesions in one session, with reported recurrence rates of 2 to 5 percent [78,82]. It may be used for destroying or cutting the lesion while coagulating the base. CO₂ laser used in cutting mode may provide a specimen suitable for histologic examination; however, this mode provides no advantage with respect to scarring. In a review of 102 PGs treated with CO₂ laser, five recurred.

The long-pulsed 1064 nm Nd:YAG laser can be used following biopsy excision of PG and is suggested as a modality for difficult-to-treat locations, such as the extremities or nail matrix, or for larger sessile PG [84,87]. In a review of 20 patients with PG treated with excisional biopsy followed by Nd:YAG, clearance was obtained in 19 of the patients after one to four treatment sessions. One patient did not respond and was ultimately treated with CO₂ laser. Slight residual textural changes, but no visible scars, were noted in 53 percent of the treated patients [84].

●Cryotherapy – Cryotherapy with liquid nitrogen has been described as a treatment for small PGs with a low risk of recurrence, scar formation, and hypo- or hyperpigmentation [79,80]. However, we generally do not suggest cryotherapy because multiple treatments may be necessary, and cryotherapy does not permit histologic confirmation:

•In a review of 185 PGs, the recurrence rate for lesions treated with one or multiple liquid nitrogen applications was 1.6 percent (table 1) [78].

•In a prospective study, 135 children and adults with a clinical diagnosis of PG were treated with liquid nitrogen. Resolution of the lesion was obtained in all patients after one to four treatment sessions, with minimal scar or hyperpigmentation [80].

•One small, randomized trial compared cryotherapy (47 patients) with curettage and electrodessication of the base (42 patients) for PG [79]. After one treatment, resolution was reported in 63 percent of patients in the cryotherapy group versus 97 percent of those in the curettage group. Scar and/or hypo- or hyperpigmentation were reported in 43 percent of patients in the cryotherapy group and 31 percent of patients in the curettage group. These results should be interpreted with caution, however, because typical cryotherapy regimens usually involve more than one treatment.

●Topical and intralesional therapies – For adults and older pediatric patients, we generally do not suggest topical or intralesional therapies. Drawbacks of these modalities are the inability to perform histologic examination and, for some, a high recurrence rate. An exception may be young pediatric patients in whom histologic confirmation is less essential because the risk for malignant mimickers is very low. Topical therapies may be attempted first in this group to avoid potentially fear-inducing procedures:

•Topical beta blockers – Topical beta blockers, including topical propranolol and timolol, a nonselective beta-adrenergic antagonist, have been used to treat PG in a small number of children and adults with favorable results [88-90]:

-In a series of six children with recurrent or primary diagnosis of PG, timolol 0.5% solution applied two to three times a day induced at least a partial response by two months [88].

-In another series of 18 children with PG, 4% topical propranolol gel induced complete resolution in 11 children and almost complete resolution in 2 children [91].

-Topical 1% propranolol ointment with occlusion used for 14 to 150 days induced complete lesion regression in 13 of 22 children with PG [92].

-In a small study of 10 adult patients with periungual PG, propranolol 1% cream applied overnight under occlusion for 30 to 45 days induced complete resolution of all lesions located on the fingernails, including those secondary to targeted chemotherapy for cancer [89]. However, topical propranolol was not effective for PGs located on the toenails.

-In a series of 17 patients with ocular PG, timolol 0.5% solution applied twice daily for two to six weeks induced a complete resolution in 15 patients after a mean treatment duration of three weeks [93].

-In a retrospective analysis of topical treatments used to treat PG at a single site, 16 patients were prescribed topical timolol 0.5% solution and compared with 14 patients given ultra-potent topical corticosteroids [94]. Both treatments were applied twice daily for a median of five and six weeks, respectively. In both groups, 50 percent of the patients experienced partial or complete resolution. Subsequent excision was performed in 56 percent of the patients treated with timolol and 43 percent of those treated with corticosteroids.

•Sclerotherapy – Sclerotherapy with injection of ethanolamine oleate, sodium tetradecyl sulfate, or polidocanol has been described in a small series of patients, with complete resolution and inconspicuous scarring [95-98]. A rare but potentially serious side effect of sclerotherapy is cutaneous necrosis, resulting from sclerosant extravasation or direct injection in a cutaneous arteriole. (See "Injection sclerotherapy techniques for the treatment of telangiectasias, reticular veins, and small varicose veins".)

•Chemical cauterization – Silver nitrate has been used in a small series of patients with PG on the hand [99]. The mass was removed bluntly, and the base of the lesion was cauterized with silver nitrate. Complete resolution was reported in 11 patients after one to three treatments. Burning of the normal skin is a potential adverse effect of cauterization with silver nitrate.

•Topical phenol – Topical phenol has been used for treatment of periungual PG [100]. A piece of cotton dipped in phenol 98% solution is placed over the PG for three one-minute applications, repeated weekly until resolution. In a case series of 18 patients, 1 to 13 sessions were needed for clearance [100]. Recurrence is more common with topical phenol than with surgical procedures. However, phenol application may be a treatment option for patients who refuse surgery or for smaller periungual PG.

•Topical imiquimod – Topical imiquimod has been used to treat PG in children and adults [101-105]. Treatment regimens are variable, ranging from 6 days to 17 weeks (average 40 days), with frequency of application from three times per week up to two times per day, as tolerated. In a series of 10 children treated with topical imiquimod, one treatment failure was reported; no recurrence occurred in children responding to treatment during a follow-up of approximately 10 months [102]. Side effects of imiquimod include irritation, erythema, skin necrosis, and secondary infection.

•Suture ligation – Ligation of the lesion base using soft (absorbable) suture material has been used in children with facial PG [106-108]. Following ligation, the tumor becomes necrotic and falls off in days to weeks.

•Intralesional injection – Intralesional injection of bleomycin, corticosteroids, or absolute ethanol is described in a small number of case reports [109-112].

•Topical table salt – The use of common table salt applied directly to the PG has been described as a noninvasive treatment option that may be suitable for children, pregnant individuals, patients adverse to surgical procedures, or recurrence of a PG [113]. In a series of 50 patients, complete resolution was reported in 100 percent of patients after a mean 14.77 days of treatment (range 6 to 38 days) [114].

Lesions in cosmetically sensitive areas — Full-thickness surgical excision and suturing may not be desirable for PGs located in cosmetically or functionally challenging areas due to the risk of scarring and/or functional impairment. Alternative approaches include:

●For adults and older children who can tolerate local anesthesia, we suggest shave excision followed by cauterization or laser photocoagulation of the lesion base. This treatment modality results in less conspicuous scarring while providing a tissue specimen for histopathologic examination.

●For young children with small PG located in cosmetically sensitive areas, lesion destruction with electrocautery or PDL or CO₂ laser photocoagulation, if available, are reasonable options [4,81]. Topical therapies, such as beta blockers or imiquimod (see 'Other treatments' above), could be initiated first to reduce the size of the lesion or, in some cases, to completely resolve the PG prior to attempting laser or electrocautery [88,91,92,102]. In young children, it is less important to have histologic confirmation because the risk of malignant mimics of PG is much lower than in adults. However, the need for sedation or general anesthesia is a concern, especially if multiple treatment sessions are necessary. Multiple treatment sessions are usually required with PDL because of the limited penetration of PDL in the dermis; the CO₂ laser generally removes PG lesions in one session [79]. In a series of 22 children with small PG (average size 4 mm) treated with PDL, 15 required two to six laser treatments [81]. Twenty patients responded to treatment and healed without scarring, and two patients underwent subsequent shave excision and electrocautery. PDL and other vascular lasers may leave hypo- or hyperpigmentation. (See "Laser and light therapy for cutaneous vascular lesions".)

Special situations

Recurrent lesions — Surgical excision is the treatment of choice for PGs that recur after treatment with shaving or nonsurgical modalities.

Multiple or disseminated lesions — For patients with multiple or disseminated PG, we suggest surgical excision of a few lesions for histopathologic confirmation, followed by observation for spontaneous regression of the remaining lesions to avoid unnecessary scar formation [58]. Medical therapy with oral or topical beta blockers (eg, timolol ophthalmic solution, propranolol cream) has been used in a few pediatric patients with agminated (grouped multiple) PGs, in patients with multiple periungual PGs induced by treatment with epidermal growth factor receptor (EGFR) inhibitors, and an adult with disseminated PG [60,115-117].

Periungual lesions — Drug-induced periungual PGs (picture 23) may regress after the discontinuation of the offending drug. When drug discontinuation is not an option, these lesions can be treated conservatively with a short course of high-potency topical corticosteroids and topical antibiotics [17,30]. Benefit with topical beta blockers has been reported in patients with periungual PGs induced by treatment with EGFR inhibitors [116].

Periungual PGs that do not respond to topical treatment and lesions unrelated to medications can be treated with surgical excision, curettage, or other destructive therapy. Histopathologic examination to exclude malignancy is advised prior to proceeding to destructive treatments:

●In a series of 58 patients with periungual or subungual PG, successful treatment included removal of the causative agent if known (eg, foreign bodies or medications) and a two to three week course of high-potency topical corticosteroids followed by curettage or nail avulsion and curettage for lesions of the nail bed [17].

●In a series of 25 patients treated with EGFR inhibitors who developed paronychia and periungual PGs, complete or partial response was seen in 22 patients (88 percent) who were treated with photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT) repeated every three weeks for three times [118].

●In a series of 11 patients treated with EGFR inhibitors who developed periungual PGs and ingrown nails, the use of plastic tubing, referred to as the "gutter method," to separate the nail and lateral nail fold served as adjunctive therapy to cryotherapy and/or topical steroids to reduce pain [119].

Intraoral lesions — Surgical excision down to the periosteum is the treatment of choice for intraoral PGs [47,120]. CO₂ laser and diode laser excision may be an alternative to surgical excision for removing PG of the oral cavity [121-123].

PROGNOSIS — Recurrence rates following treatment range from 0 to 15 percent, depending upon the modality of therapy and location of the pyogenic granuloma (PG) (table 1) [3,4]. (See 'Management' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vascular anomalies".)

SUMMARY AND RECOMMENDATIONS

●Definition and epidemiology – Pyogenic granuloma (PG) or lobular capillary hemangioma is a benign vascular tumor of the skin or mucous membranes characterized by rapid growth and friable surface. PG occurs in patients of all ages, with a peak incidence in the second and third decades of life. (See 'Epidemiology' above.)

●Clinical presentation – PG presents as a small, red papule that grows rapidly over weeks to months and then stabilizes (picture 2A-B, 3D-E). The lesions may be pedunculated or sessile, with a characteristic epithelial collarette at the base (picture 3B). The surface is friable, bleeds profusely after minor trauma, and may become ulcerated. PGs are usually solitary, but multiple satellite lesions and disseminated forms also occur. (See 'Clinical presentation' above.)

●Pathology – Histologically, PG consists of a proliferation of capillary vessels with stromal edema and a mixed inflammatory infiltrate (picture 7A-B). (See 'Pathology' above.)

●Diagnosis – The diagnosis of PG is usually straightforward, based upon the clinical history of an erythematous, dome-shaped papule that bleeds easily and has developed over a few days to weeks (picture 3C, 3E). However, histologic confirmation is always desirable because several benign and malignant lesions can mimic PG. (See 'Diagnosis' above.)

●Treatment – Treatment is usually required for PG because of frequent ulceration and bleeding. There are few randomized trials comparing treatments for PG, and there is no consensus regarding the optimal approach (see 'General considerations' above):

•Noncosmetically sensitive areas – For PG located in noncosmetically sensitive areas in adults and children who can tolerate local anesthesia, we suggest surgical excision rather than destructive or topical treatments (Grade 2C). For nonpedunculated (sessile) PG, a narrow, elliptical excision of skin to the subcutaneous fat beneath the lesion followed by wound closure with sutures is appropriate to control bleeding and minimize the risk of recurrence. Pedunculated lesions can be removed with shave excision or curettage followed by electrocautery or laser photocoagulation of the base. (See 'Lesions in noncosmetically sensitive areas' above and 'Surgical excision' above.)

•Cosmetically sensitive areas – For PG located in cosmetically sensitive areas in adults and older children who can tolerate local anesthesia, we suggest shave excision followed by cauterization or laser photocoagulation of the lesion base (Grade 2C). This treatment modality results in less conspicuous scarring while providing a tissue specimen for histopathologic examination.

In young children with small PG located in cosmetically sensitive areas, lesion destruction with electrocautery or pulsed dye laser (PDL) or carbon dioxide (CO₂) laser photocoagulation, if available, is a reasonable option. In young children, it is less important to have histologic confirmation because the risk of malignant mimics of PG is much lower than in adults. However, the need for sedation or general anesthesia is a concern, especially if multiple treatment sessions are necessary. Alternatively, topical therapies, such as topical beta blockers, can be initiated first to reduce the size or even resolve the lesion prior to attempting laser or electrocautery. (See 'Lesions in cosmetically sensitive areas' above.)

•Recurrent pyogenic granuloma – For PGs that recur after treatment with shaving or nonsurgical modalities, surgical excision is the treatment of choice. (See 'Recurrent lesions' above.)