AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Granuloma annulare (GA) is a benign self-limited dermatosis characterized by a raised annular configuration.

Pyogenic granuloma (PG) is misnamed, being neither pyogenic nor granuloma. It is a benign, acquired, vascular tumor of the skin and mucous membrane that appears as a rapidly growing vascular papule or nodule. Sometimes it appears at the site of a previous penetrating injury. PG is often observed in infancy and childhood but also may be observed in adults, particularly in pregnant women.

Pathophysiology

GA may be localized, generalized, perforating, or subcutaneous. Lesions of the first 3 presentations have similar appearances, but each one follows a distinctive clinical course. Subcutaneous GA appears differently, as it is a disease of childhood in which deep dermal or subcutaneous nodules lie on or near the periosteum and are distributed on the feet, lower legs, fingers, hands, forearms, scalp, and forehead.

PG is a disorder of angiogenesis whose underlying etiology remains unknown. A predilection exists for the head and neck, although lesions may appear on any part of the body. Purplish, pulpy, vascular lesions of PG often involve the gum and other mucous membranes of the mouth.

Frequency

United States

GA is most common in children and young adults. Solitary PG is common and represents 0.5% of all skin nodules in children.

Mortality/Morbidity

• GA is a self-limited cosmetic disease without any systemic medical complications. On rare occasions, it may involve fascia and tendons and may cause sclerosis, lymphedema, and deformities such as joint ankylosis. GA has been epidemiologically linked to diabetes mellitus, necrobiosis lipoidica diabeticorum, and rheumatoid nodules.
• PG is a benign vascular tumor, mostly occurring in childhood. Lesions may bleed and ulcerate.

Race

• GA is believed to affect patients without respect to racial heritage.
• PG may affect white populations more than other racial groups, but this is not well proven and the observation may reflect sampling bias.

Sex

GA has a slight tendency toward females.

• In GA, females are slightly more affected than males.
• In PG, the male-to-female ratio is 3:2.

Age

• More than two thirds of patients with GA experience disease onset when younger than 30 years. In pediatric patients with GA, the age of onset ranges from 1-14 years, with a mean of 4 years. The localized type of GA occurs primarily in young children, whereas the generalized form is seen in patients younger than 10 years or older than 40 years.
• Approximately one half of cases of PG occur within the first 5 years of life.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Granuloma annulare
• • History should focus on issues regarding diet, weight loss, and/or fever. This will help rule out other potential diagnoses such as trauma, infection, tumor, metabolic bone or skin disease, and inflammatory or autoimmune disease.
  • Children with GA are usually otherwise healthy and have the lesions for several months without any other symptoms.
• Pyogenic granuloma
• • In patients with suspected PG, history should focus on the onset and associated symptoms of the rash.
  • Query the patient or parents regarding a preceding history of trauma, viral or bacterial infection, pregnancy, or HIV infection.
  • The patient and family should be questioned regarding prior rashes, port wine stain, and prior treatment.
  • The presence or absence of signs such as bleeding or ulceration should be noted.

Physical

• Granuloma annulare
• • Children with GA usually present with one or more firm, nontender soft tissue nodules on the extremities, scalp, or forehead.
  • Papules are 1-5 mm in diameter, flesh-colored or slightly pink, and smooth rather than scaly. They are easily distinguished from the lesions of erythema chronicum migrans, which are usually red in color and ring-shaped with central clearing.
  • Lesions may be generalized in children or in immunocompromised patients but are most often found along the extensor aspects of the extremities, in close proximity to joints.
  • Nodules of the scalp or forehead usually are fixed to periosteum and are only minimally mobile. Lesions of the extremities usually are fixed to fascia and are freely mobile.
• Pyogenic granuloma
• • Physical examination should focus on the location and size of vascular papules, nodules, and peduncles that may be present on the skin or mucous membranes.
  • The presence or absence of bleeding or ulceration should be noted.
  • If present, other rashes should be described.

Causes

• Granuloma annulare
• • Etiology of childhood GA is unknown.
  • No good evidence supports suggestions that trauma, tuberculosis, streptococcal infection, herpes zoster/varicella, collagen vascular disorder, or diabetes mellitus are causally related to GA. There are also weak associations with BCG vaccination, drugs such as allopurinol, zalcitabine, other viral infections such as EBV, HIV, Hepatitis C, parvovirus B19, autoimmune thyroiditis and malignant conditions.
  • There is some evidence to suggest that GA is an immunologic disease in the form of delayed type hypersensitivity reaction.
• Pyogenic granuloma
• • The cause of PG is unknown.
  • Suggested potential risk factors include pregnancy, birth control pills, bacterial and viral infections, microscopic arteriovenous anastomoses, and angiogenic growth factors, but no good evidence supports any of these as primary causative factors. In one large pediatric series, only 7% had any history of trauma preceding the development of the lesion.
  • PGs have been reported arising within port wine stains. On rare occasions, lesions have been associated with malignancy.
  • Intraoral lesions can have an appearance and behavior very similar to the appearance and behavior of intraoral Kaposi sarcoma. These lesions may bleed extensively if biopsied; thus, HIV testing may be indicated when patients have intraoral lesions with the appearance of PG.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Amelanotic melanoma (PG)
Amyloidosis
Annular elastolytic granuloma
Annular lichen planus
Bacillary angiomatosis (PG)
Creeping eruption
Erythema annulare centrifugum
Erythema chronicum migrans
Erythema elevatum diutinum
Fibrosarcoma (PG)
Granuloma multiforme
Kaposi sarcoma
Lipoid proteinosis
Majocchi granuloma
Metastatic lesions (PG)
Necrobiosis lipoidica
Peripheral giant cell granuloma (PG)
Peripheral ossifying fibroma (PG)
Ringworm
Rheumatoid nodules
Squamous cell carcinoma (PG)
Subacute lupus erythematosus
Tuberculous granulomas
Verrucous carcinoma (PG)
Verruca plana
Xanthomas

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory studies may be helpful if the diagnosis of GA cannot be ruled out with a complete history emphasizing issues such as diet, weight loss, and/or fever. If an accurate history is unobtainable, a CBC and erythrocyte sedimentation rate (ESR) should be obtained.
• No laboratory studies are needed to make the diagnosis of PG. CBC, human chorionic gonadotropin (HCG), HIV, and biochemical profiles are needed only if there is concern for other etiologies.
• Check blood glucose if there is concern of diabetes mellitus and GA.
• Check rheumatoid factor if symptoms of rheumatoid arthritis are present.

Imaging Studies

• Granuloma annulare
• • Radiographs are not necessary for diagnosis of GA but may be helpful if other problems are suspected.
  • In GA, the lesion is soft tissue mass without any calcification or bony involvement.
• Pyogenic granuloma: Imaging studies are not useful in PG.

Procedures

• Skin biopsy
• • To obtain a specimen, a 22- or 24-gauge needle may be gently passed tangentially just below the superficial capsular layer of the lesion, then flushed with saline to yield a small but adequate specimen.
  • Skin biopsy is diagnostic for GA. Because the lesions regress, biopsy is needed only when a definitive diagnosis is required.
  • Skin biopsy is also diagnostic for PG.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Granuloma annulare: Prehospital care is not a consideration for patients with GA, which is a nuisance lesion.
• Pyogenic granuloma
• • Patients with PG may present with acute bleeding from the vascular lesions, particularly when they are intraoral.
  • In the prehospital setting, bleeding should be controlled by direct pressure, and the airway should be secured if necessary.
  • IV access may be indicated if hemorrhage is severe.

Emergency Department Care

• Granuloma annulare
• • GA rarely requires any treatment since spontaneous resolution is common.
  • Medical and surgical interventions should be avoided unless absolutely necessary.
• Pyogenic granuloma
• • For patients who present with hemorrhage, bleeding often may be controlled with direct pressure.
  • A vasoconstrictor packing (eg, cocaine or tetracaine with adrenaline) sometimes may be needed.
  • When bleeding is refractory or recurrent, sclerotherapy by direct injection of 1-2 mL of 1% sodium tetradecyl sulfate into the vascular plexus is usually effective and may even provide a definitive cure.
  • Compress the lesion for 15 minutes following injection. Sclerotherapy usually is necessary in order to allow time for the tumor vessels to go into spasm.
  • Effective treatment includes excision (although this may be difficult if the lesion is extensive), electrodesiccation, curettage, chemical cauterization, and injection sclerotherapy. Carbon dioxide and argon lasers have been used successfully for superficial cases of PG. Pulsed-dye laser also has been shown effective in the treatment of PGs when the lesion is superficial and of less than 0.5 cm thickness. Advantages of excision and electrocautery are ease of use and lack of recurrences according to 1 recent study in children.

Consultations

• If diagnosis is unproven, follow-up care with a dermatologist is indicated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Granuloma annulare

Medical treatments such as corticosteroids, potassium iodide, dapsone, niacinamide, chlorambucil, and isotretinoin have been tried, but none has been shown efficacious. Other treatments include liquid nitrogen cryotherapy, oral and topical PUVA photochemotherapy, UVA1 phototherapy, and cyclosporin. Isotretinoin should be reserved for patients with disseminated or refractory GA because of potential serious toxicity.

Drug Category: Corticosteroids

Used for their potent anti-inflammatory activity.

Drug Category: Antioxidants

Isotretinoin may have proliferative and inhibitory effects on collagen synthesis that may ameliorate symptoms associated with GA.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Further outpatient care is needed to follow the progress of lesions because as many as 20% of children with GA experience recurrence.
• Local recurrence after treatment of PG by any method is not uncommon. In a recent series, the majority of patients with uncomplicated PG were treated with single shave excision and electrocautery, with no recurrences.

In/Out Patient Meds

• GA is a self-limited cosmetic disease that rarely needs treatment and rarely produces sequelae.
• Many drug therapies have been proposed, but none are known to be efficacious. No outpatient medications are used for the treatment of PG, which is usually managed by extirpation.

Complications

• In cases of GA without other etiology of the subcutaneous nodules, no complications are encountered.
• The principal complication associated with PG is hemorrhage, which can be significant and can require intervention.

Prognosis

• The prognosis of GA is excellent, as the lesions usually regress spontaneously. Fifty to 70% with the localized type resolve after 1-2 years. The generalized type is less likely to resolve spontaneously.
• The prognosis of PG is also excellent.

Patient Education

• Reassurance and referral are the principal and essential steps in patient education.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Pyogenic granuloma in pregnancy
• • PG is common in pregnancy, with intraoral mucosal lesions appearing in 5% of pregnancies and in some unknown fraction of patients taking oral contraceptives.
  • Although the tumor mass often regresses after delivery or in response to adjustment of the contraceptive medication, spontaneous recurrences may be observed.
  • Etiology in pregnant women may be related to gingival inflammation, as the prevalence is reported to be less in patients with better oral hygiene.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Arroyo MP. Generalized granuloma annulare. Dermatol Online J. Oct 2003;9(4):13. [Medline].
• Dillman AM, Miller RC, Hansen RC. Multiple pyogenic granulomata in childhood. Pediatr Dermatol. Mar 1991;8(1):28-31. [Medline].
• Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics. Dec 1997;100(6):965-7. [Medline].
• Grimalt R, Caputo R. Symmetric pyogenic granuloma. J Am Acad Dermatol. Oct 1993;29(4):652. [Medline].
• Looney M, Smith KM. Isotretinoin in the treatment of granuloma annulare. Ann Pharmacother. Mar 2004;38(3):494-7. [Medline].
• Medlock MD, McComb JG, Raffel C, Gonzalez-Gomez I. Subcutaneous palisading granuloma of the scalp in childhood. Pediatr Neurosurg. 1994;21(2):113-6. [Medline].
• Mooney MA, Janniger CK. Pyogenic granuloma. Cutis. Mar 1995;55(3):133-6. [Medline].
• Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatr Dermatol. Jan-Feb 2004;21(1):10-3. [Medline].
• Pomeranz AJ, Fairley JA. The systematic evaluation of the skin in children. Pediatr Clin North Am. Feb 1998;45(1):49-63. [Medline].
• Sills ES, Zegarelli DJ, Hoschander MM, Strider WE. Clinical diagnosis and management of hormonally responsive oral pregnancy tumor (pyogenic granuloma). J Reprod Med. Jul 1996;41(7):467-70. [Medline].
• Tan HH, Goh CL. Granuloma annulare: a review of 41 cases at the National Skin Centre. Ann Acad Med Singapore. Nov 2000;29(6):714-8. [Medline].
• Tay YK, Weston WL, Morelli JG. Treatment of pyogenic granuloma in children with the flashlamp-pumped pulsed dye laser. Pediatrics. Mar 1997;99(3):368-70. [Medline].

Article Last Updated: Jun 13, 2006