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.
View Image | Solitary, well-demarcated, brown-red plaque associated with granuloma faciale. |
View Image | 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.
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.
View Image | Solitary, well-demarcated, brown-red plaque associated with granuloma faciale. |
View Image | Solitary, well-demarcated, brown-red plaque associated with granuloma faciale. |
View Image | Solitary, well-demarcated, brown-red plaque associated with granuloma faciale. |
View Image | 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]
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.[12] 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.
View Image | Histologic findings in granuloma faciale. |
View Image | Histologic findings in granuloma faciale. |
View Image | Histologic findings in granuloma faciale include a normal epidermis; a grenz zone of uninvolved dermis just beneath the epidermis; and a dense, polymo.... |
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.[13] 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.[14]
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.
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:
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 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.[22] Pulsed-dye laser[4, 23, 24] 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,[25] ), intralesional gold injections, oral bismuth, antimalarials, isoniazid, oral potassium arsenite, p-aminobenzoic acid (PABA), calciferol, topical psoralen UV-A (PUVA),[26] intralesional rituximab,[27] and radiation therapy. More recently, topical tacrolimus has been reported of benefit.[28, 29, 30] Granuloma faciale can also be treated with another topical calcineurin inhibitor, pimecrolimus cream.[31] Dapsone is the oral medication most frequently reported to be of some benefit.[32, 33, 34] Rituximab is a monoclonal antibody against CD-20 approved by the US Food and Drug Administration for treatment of some autoimmune and tumoral diseases.
Dapsone (Avlosulfon)
Clinical Context:
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)
Clinical Context:
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.
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Tacrolimus ointment (Prograf)
Clinical Context:
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)
Clinical Context:
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.
Author
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School
Disclosure: Nothing to disclose.
Coauthor(s)
Michael Wiederkehr, MD, Consulting Staff, Livingston Dermatology Associates; Consulting Staff, Comprehensive Dermatology and Laser Center
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Paul Krusinski, MD, Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center
Disclosure: Nothing to disclose.
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