eMedicine Specialties > Emergency Medicine > Dermatology

Granuloma, Annulare and Pyogenic

Richard Lichenstein, MD, Associate Professor, Pediatric Emergency Department, University of Maryland School of Medicine

Updated: Sep 18, 2008

Introduction

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

Granuloma annulare 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 granuloma annulare 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.

Pyogenic granuloma 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 pyogenic granuloma often involve the gum and other mucous membranes of the mouth.

Frequency

United States

Granuloma annulare is most common in children and young adults.

Solitary pyogenic granuloma is common and represents 0.5% of all skin nodules in children.

Mortality/Morbidity

• Granuloma annulare 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. Granuloma annulare has been epidemiologically linked to diabetes mellitus, necrobiosis lipoidica diabeticorum, and rheumatoid nodules.
• Pyogenic granuloma is a benign vascular tumor, mostly occurring in childhood. Lesions may bleed and ulcerate.

Race

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

Sex

Granuloma annulare has a slight tendency toward females.

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

Age

• More than two thirds of patients with granuloma annulare experience disease onset when younger than 30 years. In pediatric patients with granuloma annulare, the age of onset ranges from 1-14 years, with a mean of 4 years. The localized type of granuloma annulare 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 pyogenic granuloma occur within the first 5 years of life.

Clinical

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 granuloma annulare are usually otherwise healthy and have the lesions for several months without any other symptoms.
• Pyogenic granuloma
  • In patients with suspected pyogenic granuloma, 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.

For a CME/CE activity, see Examining the Ears, Nose, and Oral Cavity in the Older Patient.

Causes

• Granuloma annulare
  • Etiology of childhood granuloma annulare 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 granuloma annulare. There are also weak associations with BCG vaccination; drugs such as allopurinol and zalcitabine; other viral infections such as EBV, HIV, hepatitis C, Parvovirus B19; autoimmune thyroiditis; and malignant conditions. Borrelia has also recently been implicated in one study.¹
  • There is some evidence to suggest that granuloma annulare is an immunologic disease in the form of delayed type hypersensitivity reaction.
• Pyogenic granuloma
  • The cause of pyogenic granuloma 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.
  • Pyogenic granulomas 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 pyogenic granuloma.

Differential Diagnoses

Bites, Insects
Catscratch Disease
Erythema Multiforme
Syphilis
Tick-Borne Diseases, Lyme
Tinea

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

Laboratory Studies

• Laboratory studies may be helpful if the diagnosis of granuloma annulare 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 pyogenic granuloma. CBC, human chorionic gonadotropin (HCG), HIV, and biochemical profiles are needed only if there is concern for other etiologies.
• Check blood glucose level if there is concern of diabetes mellitus and granuloma annulare.
• Check rheumatoid factor if symptoms of rheumatoid arthritis are present.

Imaging Studies

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

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 granuloma annulare. Because the lesions regress, biopsy is needed only when a definitive diagnosis is required.
  • Skin biopsy is also diagnostic for pyogenic granuloma.

Treatment

Prehospital Care

• Granuloma annulare: Prehospital care is not a consideration for patients with granuloma annulare, which is a nuisance lesion.
• Pyogenic granuloma
  • Patients with pyogenic granuloma 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
  • Granuloma annulare 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 pyogenic granuloma. Pulsed-dye laser also has been shown effective in the treatment of pyogenic granulomas 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 one recent study in children.

Consultations

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

Medication

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.²

Corticosteroids

Used for their potent anti-inflammatory activity.

Triamcinolone acetonide (Aristospan)

Treats inflammatory lesions that are responsive to steroids. Decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.

Dosing

Adult

2.5-40 mg intralesionally (10 mg/mL or 40 mg/mL solutions) and repeat prn

Pediatric

Administer as in adults

Interactions

Coadministration with barbiturates, phenytoin, and rifampin decreases effects of triamcinolone

Contraindications

Documented hypersensitivity; fungal, viral, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur; abrupt discontinuation of glucocorticoids may cause adrenal crisis

Retinoids

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

Isotretinoin (Amnesteem, Claravis, Sotret)

Has been used as chemoprophylaxis of skin cancers

Dosing

Adult

20-40 mg PO qd; some reports suggest 0.5-1 mg/kg/d PO

Pediatric

Not established

Interactions

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; isotretinoin may reduce plasma levels of carbamazepine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur
Diabetic patients may experience problems in controlling their blood sugar while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur; mood swings or depression may occur; caution if history of depression

Follow-up

Further Outpatient Care

• Further outpatient care is needed to follow the progress of lesions because as many as 20% of children with granuloma annulare experience recurrence.
• Local recurrence after treatment of pyogenic granuloma by any method is not uncommon. In a one series, most of patients with uncomplicated pyogenic granuloma were treated with single shave excision and electrocautery, with no recurrences.³

Inpatient & Outpatient Medications

• Granuloma annulare 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 pyogenic granuloma, which is usually managed by extirpation.

Complications

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

Prognosis

• The prognosis of granuloma annulare 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 pyogenic granuloma is also excellent.

Patient Education

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

Miscellaneous

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

1. Ziemer M, Grabner T, Eisendle K, Baltaci M, Zelger B. Granuloma annulare - a manifestation of infection with Borrelia?. J Cutan Pathol. Jun 18 2008;[Medline].

2. Looney M, Smith KM. Isotretinoin in the treatment of granuloma annulare. Ann Pharmacother. Mar 2004;38(3):494-7. [Medline].

3. Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatr Dermatol. Jan-Feb 2004;21(1):10-3. [Medline].

4. Arroyo MP. Generalized granuloma annulare. Dermatol Online J. Oct 2003;9(4):13. [Medline].

5. Dillman AM, Miller RC, Hansen RC. Multiple pyogenic granulomata in childhood. Pediatr Dermatol. Mar 1991;8(1):28-31. [Medline].

6. Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics. Dec 1997;100(6):965-7. [Medline].

7. Grimalt R, Caputo R. Symmetric pyogenic granuloma. J Am Acad Dermatol. Oct 1993;29(4):652. [Medline].

8. 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].

9. Mooney MA, Janniger CK. Pyogenic granuloma. Cutis. Mar 1995;55(3):133-6. [Medline].

10. Pomeranz AJ, Fairley JA. The systematic evaluation of the skin in children. Pediatr Clin North Am. Feb 1998;45(1):49-63. [Medline].

11. Scheinfeld NS. Pyogenic granuloma. Skinmed. Jan-Feb 2008;7(1):37-9. [Medline].

12. 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].

13. 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].

14. 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].

Keywords

granuloma annulare, pyogenic granuloma, skin nodule, GA, dermatosis, PG, vascular tumor of skin and mucous membrane, papule, nodule, peduncle, subcutaneous GA, self-limited dermatosis, disorder of angiogenesis, sclerosis, lymphedema, joint ankylosis, necrobiosis lipoidica diabeticorum, rheumatoid nodules, benign vascular tumor

Contributor Information and Disclosures

Author

Richard Lichenstein, MD, Associate Professor, Pediatric Emergency Department, University of Maryland School of Medicine
Richard Lichenstein, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Edward A Michelson, MD, Program Director, Associate Professor, Department of Emergency Medicine, University Hospital Health Systems in Cleveland
Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Mark W Fourre, MD, Program Director, Department of Emergency Medicine, Maine Medical Center; Associate Clinical Professor, Department of Surgery, University of Vermont School of Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center
Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

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