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AUTHOR AND EDITOR INFORMATION

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Author: Michael Wiederkehr, MD, Consulting Staff, Livingston Dermatology Associates

Michael Wiederkehr is a member of the following medical societies: American Medical Association

Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Editors: Daniel J Hogan, MD, Director of Bay Pines Dermatology Residency Program, Bay Pines Veterans Affairs Healthcare System; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center

Author and Editor Disclosure

Synonyms and related keywords: GF, granuloma faciale eosinophilicum, granuloma faciale with eosinophilia

INTRODUCTION

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Background

Granuloma faciale (GF) is an uncommon benign chronic skin disease of unknown origin characterized by single or multiple cutaneous nodules, usually occurring over the face. Occasionally, extrafacial involvement is noted, most often on sun-exposed areas. Lever and Leeper first recognized GF as a distinct entity in 1950. Pinkus' group suggested the name granuloma faciale that same year. The disease mimics many other dermatoses and can be confused with conditions, such as sarcoidosis, discoid lupus erythematosus, mycosis fungoides, and fixed drug eruption.

Pathophysiology

The skin is the primary organ system that is affected. Reports of GF-like lesions of the oral mucosa are rare.

Frequency

United States

Cases of GF are rare.

Race

GF is found most commonly in whites; however, it has been reported rarely in Japanese and blacks.

Sex

Men are affected more frequently than women.

Age

GF is primarily a disease of middle age (median age, 45 y).


CLINICAL

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History

  • GF is usually asymptomatic.
  • It rarely may be tender or cause itching or stinging.
  • Lesions may darken upon sun exposure.

Physical

  • Solitary or, more commonly, multiple, soft, elevated, and well-circumscribed papules, plaques, or nodules are observed.
  • Lesions are most commonly located over the face. Reported extrafacial locations include the scalp, the trunk, and the upper and lower extremities.
  • The size of the lesions varies from a few millimeters to several centimeters in diameter.
  • The color varies from shades of dull red to brown, blue, and purple.
  • Lesions have a smooth surface with prominent follicular orifices (peau d'orange) and may be covered by telangiectases.

Causes

  • Some cases are idiopathic.
  • A gamma interferon–mediated process has been suggested.
  • Sun exposure may play a role.
    • Sunlight-exposed areas are more commonly affected than non–sun-exposed areas.
    • Lesions may darken with sunlight exposure.


DIFFERENTIALS

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Acute Febrile Neutrophilic Dermatosis
Alopecia Mucinosa
Amyloidosis, Nodular Localized Cutaneous
Angiolymphoid Hyperplasia with Eosinophilia
Cutaneous T-Cell Lymphoma
Drug-Induced Pseudolymphoma Syndrome
Jessner Lymphocytic Infiltration of the Skin
Lupus Erythematosus, Discoid
Lymphocytoma Cutis
Pseudolymphoma, Cutaneous
Sarcoidosis

Other Problems to be Considered

Foreign body granuloma


WORKUP

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Lab Studies

  • No laboratory abnormalities are associated with GF.

Procedures

  • Obtain an adequate skin biopsy of a representative lesion.

Histologic Findings

The histologic findings of GF are diagnostic. The name granuloma faciale is a misnomer, as granulomas are never present histologically. The epidermis is unaffected. A grenz zone of uninvolved dermis is located beneath the epidermis. Below the grenz zone is a dense, polymorphous inflammatory infiltrate located most often in the papillary and mid dermis. The infiltrate consists of neutrophils, lymphocytes, eosinophils, monocytes, and, occasionally, mast cells. Vasculitic changes, including perivascular inflammation with nuclear dust and vessel wall damage, are often observed. Extravasated RBCs and hemosiderin deposition are found, which may contribute to the color of the lesions. Later, lesions may show considerable fibrosis around venules.

Direct immunofluorescence reveals immunoglobulin G, fibrin, and, occasionally, immunoglobulin M deposition at the basement membrane zone and perivascularly.

Electron microscopy reveals more perivascular eosinophils than suggested by light microscopy. Charcot-Leyden crystals, the eosinophil granules, are evident within eosinophils as well as histiocytes, providing evidence of degranulation.


TREATMENT

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Surgical Care

A variety of surgical procedures may be used in the management of GF. Scarring may occur with many of these, so the pulsed dye laser is preferred if it is available.

  • Surgical excision
  • Dermabrasion
  • Argon laser
  • Carbon dioxide laser
  • Electrosurgery
  • Cryotherapy
  • The 585-nm pulsed dye laser


MEDICATION

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GF is notoriously resistant to treatment; therefore, many different medical therapies have been tried. In addition to surgical interventions, therapeutic options that have been tried and are reported to be effective include topical corticosteroid therapy, intralesional corticosteroid injections, intralesional gold injections, oral bismuth, antimalarials, isoniazid, oral potassium arsenite, p-aminobenzoic acid (PABA), calciferol, topical psoralen UV-A (PUVA), and radiation therapy. Dapsone is the oral medication most frequently reported to be of some benefit.

Drug Category: Antimicrobial agents

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug NameDapsone (Avlosulfon)
DescriptionBactericidal and bacteriostatic against mycobacteria. Mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Has potent anti-inflammatory effects in a variety of skin disorders.
Adult Dose25-200 mg/d PO
Pediatric Dose1-2 mg/kg/d has been used in leprosy
ContraindicationsDocumented hypersensitivity; known G-6-PD deficiency; severe anemia
InteractionsMay inhibit anti-inflammatory effects of clofazimine; rifampin lowers dapsone levels 7- to 10-fold by accelerating plasma clearance; folic acid antagonists (eg, pyrimethamine) may increase hematologic reactions; probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsAdverse effects include nausea, vomiting, headache, weakness, dizziness, fatigue, nervousness, and shortness of breath; methemoglobinemia, leukopenia, hepatotoxicity, nephrotoxicity, neuropathy, psychosis, cutaneous eruptions, and hypersensitivity have all been documented with dapsone use; obtain CBC count with differential, platelet count, and reticulocyte count at baseline, weekly for a month, monthly for 6 mo, and then every month; monitor BUN, creatinine, LFTs, and urinalysis; obtain G-6-PD at baseline; hemolytic effects may be reduced by administration of vitamin E (alpha tocopherol) 400 U bid; caution in liver disease, cardiovascular disease, and renal insufficiency

Drug NameClofazimine (Lamprene)
DescriptionLipophilic rhimophenazine dye with antimicrobial and anti-inflammatory properties. Mechanism of action is unclear. Affects neutrophils and monocytes by stimulating phagocytosis and release of lysosomal enzymes and inhibits neutrophil motility and lymphocyte transformation.
Adult Dose50-300 mg/d PO
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsDapsone may inhibit anti-inflammatory action
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsMost common adverse effects are in the skin, the GI tract, and the eyes; may induce a temporary orange discoloration of the skin and the eye (cornea and conjunctivae); nausea and diarrhea are common; splenic infarction and eosinophilic enteritis are rare adverse effects; the most potentially serious adverse effect, which has been associated with months of high-dose (ie, >100 mg/d) treatment, is crystal deposition in the GI tract, which may produce a potentially fatal enteropathy; crystalline deposits have also been noted in the spleen, the liver, and the mesenteric lymph nodes


FOLLOW-UP

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Further Outpatient Care

  • Close postsurgery follow-up care is required as well as regular monitoring of patients on medications, such as dapsone.

Complications

  • Scarring may result from ablative treatment modalities.

Prognosis

  • No systemic involvement has been reported with GF. The disease is benign except for its appearance.
  • GF may persist indefinitely if untreated; spontaneous resolution rarely occurs.
  • GF has a tendency to relapse after treatment.

Patient Education

  • Inform the patient about scarring and the recurrence of the condition if an ablative procedure is performed.
  • Inform the patient about the adverse effects of medications and the need for follow-up care while taking these medications for this recalcitrant disorder.


MISCELLANEOUS

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Medical/Legal Pitfalls

  • Failure to mention the risks of scarring and recurrence if an ablative procedure is performed.
  • Failure to inform the patient of the risk of adverse effects of medications and the need to return for monitoring visits for these medications.


MULTIMEDIA

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Media file 1:  Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
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Media file 2:  Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
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Media file 3:  Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
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Media file 4:  Granuloma faciale.
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Media file 5:  Histologic findings in granuloma faciale.
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Media file 6:  Histologic findings in granuloma faciale.
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Media file 7:  Histologic findings in granuloma faciale.
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Media file 8:  Histologic findings in granuloma faciale.
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Media file 9:  Histologic findings in granuloma faciale.
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Media file 10:  Histologic findings in granuloma faciale include a normal epidermis; a grenz zone of uninvolved dermis just beneath the epidermis; and a dense, polymorphous inflammatory infiltrate located in the papillary and mid dermis. The infiltrate consists of neutrophils, lymphocytes, eosinophils, monocytes, and, occasionally, mast cells. Perivascular inflammation is also observed.
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Media file 11:  Histologic findings in granuloma faciale.
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Media file 12:  Multiple brown-red plaques on the face associated with granuloma faciale (same patient as in Images 13-16).
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Media file 13:  Multiple brown-red plaques on the nose associated with granuloma faciale (same patient as in Images 12 and 14-16).
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Media file 14:  Multiple brown-red plaques on the forehead associated with granuloma faciale (same patient as in Images 12-13 and 15-16).
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Media file 15:  Close-up view of multiple brown-red plaques on the forehead associated with granuloma faciale (same patient as in Images 12-14 and 16).
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Media file 16:  Close-up view of multiple brown-red plaques on the nose associated with granuloma faciale (same patient as in Images 12-15).
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REFERENCES

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Granuloma Faciale excerpt

Article Last Updated: Mar 22, 2006