Granuloma Faciale 

Updated: Apr 05, 2021
Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD 

Overview

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. See the images below.

Solitary, well-demarcated, brown-red plaque associ Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
Multiple brown-red plaques on the face associated Multiple brown-red plaques on the face associated with granuloma faciale.

Occasionally, extrafacial involvement is noted,[1, 2, 3, 4] most often on sun-exposed areas. Lever and Leeper first recognized granuloma faciale 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. See Sarcoidosis, Discoid Lupus Erythematosus, Mycosis Fungoides, and Fixed Drug Eruptions for more information on these topics.

Pathophysiology

The skin is the primary organ system that is affected. Reports of granuloma faciale–like lesions of the oral mucosa are rare.[5]  Eosinophilic angiocentric fibrosis may be viewed as its mucosal counterpart.[6] Innate and adaptive immunity seem to be factors in the pathogenesis of granuloma faciale.[7]

Etiology

Some cases are idiopathic.

Production of interleukin 5 by the clonal T-cell population may cause the attraction of eosinophils to the lesions.[8]

A gamma interferon–mediated process has been suggested.[9]

Sun exposure may play a role. Sunlight-exposed areas are more commonly affected than non–sun-exposed areas. Lesions may darken with sunlight exposure.

Epidemiology

Frequency

Cases of granuloma faciale are rare.

Race

Granuloma faciale 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

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

Prognosis

No systemic involvement has been reported with granuloma faciale. The disease is benign except for its appearance. Granuloma faciale may persist indefinitely if untreated; spontaneous resolution rarely occurs. Granuloma faciale 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.

 

Presentation

History

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

Physical Examination

Solitary or, more commonly, multiple, soft, elevated, and well-circumscribed papules, plaques, or nodules are observed. See the images below.

Solitary, well-demarcated, brown-red plaque associ Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
Solitary, well-demarcated, brown-red plaque associ Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
Solitary, well-demarcated, brown-red plaque associ Solitary, well-demarcated, brown-red plaque associated with granuloma faciale.
Granuloma faciale. Granuloma faciale.

Lesions are most commonly located over the face. Reported extrafacial locations include the scalp,[10] 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.[11]

Granuloma faciale may clinically resemble rhinophyma clinically.[12]

 

DDx

 

Workup

Laboratory Studies

No laboratory abnormalities are associated with granuloma faciale.

Procedures

Obtain an adequate skin biopsy of a representative lesion.

Histologic Findings

The histologic findings of granuloma faciale 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. This chronic localized fibrosing leukocytoclastic vasculitis is a vasculitic reaction pattern seen in granuloma faciale and erythema elevatum diutinum.[13] Extravasated RBCs and hemosiderin deposition are found, which may contribute to the color of the lesions. Later, lesions may show considerable fibrosis around venules. See the images below.

Histologic findings in granuloma faciale. Histologic findings in granuloma faciale.
Histologic findings in granuloma faciale. Histologic findings in granuloma faciale.
Histologic findings in granuloma faciale include a 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.

Immunophenotyping in one study documented a higher intensity of T lymphocytes than B lymphocytes, with a predominance of T CD8 lymphocytes in almost two thirds of cases, whereas other studies have tended to show the major component as T CD4 lymphocytes.[14] IgG4 was demonstrated in most, but in less than 25% of stained cells.

Direct immunofluorescence reveals immunoglobulin G (IgG), fibrin, and, occasionally, immunoglobulin M deposition at the basement membrane zone and perivascularly. Granuloma faciale in one study did not demonstrate the immunohistochemical diagnostic criteria for IgG4-related disease.[15]

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

Surgical Care

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

  • Surgical excision

  • Dermabrasion[16]

  • Argon laser[17]

  • Carbon dioxide laser[18]

  • Electrosurgery

  • Cryotherapy[19, 20, 21]

  • The 585-nm pulsed dye laser[22]

The Medscape Dermatologic Surgery Resource Center may be helpful.

Complications

Scarring may result from ablative treatment modalities.

Long-Term Monitoring

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

 

Medication

Medication Summary

Granuloma faciale is notoriously resistant to treatment; therefore, many different medical options available, with topical steroids and tacrolimus favored choices, sometimes enhanced with topical dapsone.[23, 24] Pulsed-dye laser[4, 25, 26] often produces resolution without scarring and should generally be tried before the patient is started on long-term medication. Other therapeutic options that have been tried and are reported to be effective include topical corticosteroid therapy, intralesional corticosteroid injections (without or in combination with 5-fljuorouracil,[27] ), intralesional gold injections, oral bismuth, antimalarials, isoniazid, oral potassium arsenite, p-aminobenzoic acid (PABA), calciferol, topical psoralen UV-A (PUVA),[28] intralesional rituximab,[29] and radiation therapy. More recently, topical tacrolimus has been reported of benefit.[30, 31, 32]  Granuloma faciale can also be treated with another topical calcineurin inhibitor, pimecrolimus cream.[33] Dapsone is the oral medication most frequently reported to be of some benefit.[34, 35, 36, 37] Rituximab is a monoclonal antibody against CD-20 approved by the US Food and Drug Administration for treatment of some autoimmune and tumoral diseases.

Antimicrobial agents

Class Summary

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

Dapsone (Avlosulfon)

Dapsone is bactericidal and bacteriostatic against mycobacteria. The mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. It has potent anti-inflammatory effects in a variety of skin disorders.

Clofazimine (Lamprene)

Clofazimine is a lipophilic rhimophenazine dye with antimicrobial and anti-inflammatory properties. The mechanism of action is unclear. It affects neutrophils and monocytes by stimulating phagocytosis and the release of lysosomal enzymes and inhibits neutrophil motility and lymphocyte transformation.

Calcineurin Inhibitors

Tacrolimus ointment (Prograf)

Tacrolimus reduces inflammation by suppressing the release of cytokines from T cells. It also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, it may inhibit the release of preformed mediators from skin mast cells and basophils and down-regulate the expression of FCeRI on Langerhans cells. It can be used in patients as young as 2 years. Drugs of this class are more expensive than topical corticosteroids. It is available as an ointment in concentrations of 0.03 and 0.1%.

Pimecrolimus (Elidel)

Pimecrolimus is a calcineurin inhibitor; it inhibits T-cell activation and hasa also been shown to inhibit the release of inflammatory mediators from mast cells.