Are You Confident of the Diagnosis?
What you should be alert for in the history
Although the diagnosis of granuloma faciale (GF) is difficult to establish by history alone, and is characteristically confirmed by clinical and histologic features, the following may be helpful in securing the diagnosis: The patient will often be a middle-aged white male who presents with a history of a red-brown well-circumscribed lesion present on the face for a long duration. Patients may present with cosmetic concerns only, stating no noticeable symptoms, although occasionally lesions may be pruritic.
Characteristic findings on physical examination
On physical examination, lesions of GF appear reddish, brown, or violaceous in color. Most often the lesions are solitary, but they may also be numerous and take the form of papules, nodules, or plaques. The surface of the lesion shows dilated follicular ostia.
The lesions range in size from a few millimeters to several centimeters. The face is the most common site of involvement, particularly the forehead, cheeks, and nose (Figure 1). GF is a chronic condition with a slowly progressive course and there is usually no change once the lesions are fully developed.
Rarely, extrafacial involvement of GF is observed. Such lesions usually occur months to years after the appearance of facial lesions. The most common extrafacial areas involved are the trunk and scalp. The clinical as well as histologic manifestations of extra-facial GF are identical to those of facial GF and the treatments are similar.
Expected results of diagnostic studies
There are no laboratory abnormalities associated with GF. Skin biopsy reveals an unaffected epidermis overlying a generally normal layer of dermis, referred to as the grenz zone. This is a characteristic finding in GF, but it should be noted that not all lesions show a grenz zone. Below the grenz zone is the affected dermis, which contains a dense polymorphous inflammatory infiltrate consisting of neutrophils, lymphocytes, eosinophils, monocytes, and occasionally, mast cells. Perivascular inflammation with nuclear dust and vessel wall damage along with extravasated red blood cells and hemosiderin deposition are also observed.
The term “granuloma faciale” is a misnomer, as the histological appearance does not resemble granulomatous inflammation.
Cutaneous lymphoma/lymphocytoma cutis, discoid lupus erythematosus, sarcoidosis, and basal cell carcinoma may all mimic GF clinically. The clinical distinction between these diseases and GF is made by the presence of dilated follicular ostia; however, the definitive diagnosis is primarily based on the histopathologic findings on biopsy.
Who is at Risk for Developing this Disease?
The disease is rare and found in middle-aged Caucasians. It has a predilection for males.
What is the Cause of the Disease?
The etiology of GF is not known. Several likely predisposing factors have been put forth such as allergy, trauma, actinic exposure, radiation, or an Arthus-like reaction.
Very little is known about the pathogenesis; it has been suggested that GF is an interferon-gamma-mediated process. This was established by immunophenotypic analysis of a case of GF. The analysis showed that most of the nonmyelocytic hematopoietic cells were T-helper lymphocytes. It was found that in the dermis, HECA-452 was present on most lymphocytes, which is the ligand for ELAM-1 present on vascular endothelial cells, indicating upregulation of ELAM-1, possibly by gamma-interferon production by local lymphocytes.
The upregulation of ELAM-1 allows for preferential migration of memory T-lymphocytes into the dermis. The analysis also showed the absence of ICAM-1 or HLA-DR stains in the overlying keratinocytes. The ability of dermal lymphocytes to migrate into the epidermis is mediated by the presence of ICAM-1, and its absence possibly accounts for the presence of the grenz zone.
Systemic Implications and Complications
There has been no systemic involvement reported with GF. Other than esthetic disfigurement, it is considered a benign condition.
Eosinophilic angiocentric fibrosis (EAF) has been associated in some cases with granuloma faciale. EAF is a submucosal fibrosing disorder that characteristically affects the upper airways, usually the sinonasal tract and rarely the subglottic region. It often appears as an enlarging nontender swelling with discoloration of the mucosa; the overlying skin may appear purple.
EAF and GF appear almost identical by histopathology; however, EAF has perivascular fibrosis, exhibiting a characteristic angiocentric whorling in a pattern resembling onion skin. As the fibrosis continues, it causes the mucosa to thicken and become adherent to the underlying structures. Without resolution, this leads to stenosis of the airway, which requires surgical resection.
Adjuvant therapies, such as dapsone, oral immunosuppressants, and oral as well as intralesional corticosteroids, have shown varying efficacy. Some believe that EAF is a mucosal variant of GF. The histological similarity, and the concomitant occurrence of both diseases in the same patient, are highly suggestive of a common pathologic process; however, it has yet to be proven that they are in fact variations of the same disease.
Treatment options are summarized in Table I.
|Medical Treatment||Surgical Procedures||Physical Modalities|
|Topical corticosteroids||Cryotherapy||Pulsed dye laser|
|Intralesional corticosteroids||Dermabrasion||Carbon dioxide laser|
|Tacrolimus||Surgical Excision||Argon laser|
Optimal Therapeutic Approach for this Disease
The optimal therapeutic approach begins with evaluating the severity of the GF and what effect it is having, if any, on the patient’s quality of life. Mild cases should be treated less aggressively than those causing significant disfigurement. It is important to explain to the patient the natural history of GF and the fact that most therapeutic modalities often do not work.
There is no standardized treatment for GF. Many different options are available, but nothing has shown consistent efficacy. The decision to use a specific treatment depends on what outcomes and risks are acceptable to the patient. To take advantage of any possible synergistic effect, employ a combination of therapeutic modalities.
Topical corticosteroids can be considered. Mild group VI steroids can be used. Hydrocortisone 2.5% cream daily to twice daily.
Intralesional corticosteroids have shown to be effective. Triamcinolone can be used at a concentration of 4mg/cc and 0.5cc total.
The calcineurin inhibitor tacrolimus has also shown efficacy. Tacrolimus 0.1% can be applied twice daily and should be used for several months. It upregulates IL-2 and decreases T-cell activation, leading to decreased production of IFN-gamma, possibly limiting ELAM-1 expression on dermal vascular endothelial cells and minimizing homing of lymphocytes to the dermis.
Dapsone, although an antibiotic, has shown to have potent anti-inflammatory effects in skin conditions. Adult oral dosing is recommended at 25-200mg per day. Routine blood work is necessary while on dapsone.
Pulsed dye laser using a wavelength emission of 595nm and a pulse duration of 1-3ms can be used. The treatments should be performed with 7mm minimally overlapping spots at 10-14J/cm2. The minimum time between treatments should be two months. The benefit of laser therapy is that there can be almost complete resolution of the lesion with no scarring.
Explain the natural history of GF to the patient before beginning any therapy, emphasizing the recalcitrant nature of the condition. Discuss treatment options, making clear that if one treatment method fails after adequate time is given, another option will be pursued. Emphasize that GF is not dangerous and is only a cosmetic concern.
The patient should be followed regularly to monitor therapeutic efficacy and to check laboratory studies while on dapsone. It is suggested that a complete blood count should be done once a week for the first 4 weeks, once a month for the next 6 months, and then every 6 months thereafter. Liver function tests should be taken at baseline and then checked periodically.
The patient should also be educated and watched for changes in skin pigmentation while on clofazimine. Clofazimine is known to cause pink-to-brown pigmentary changes of the skin, as well as similar discoloration in bodily fluids and secretions. The discoloration is reversible, but it may take months to years to resolve.
Unusual Clinical Scenarios to Consider in Patient Management
GF is mostly a disorder of middle-aged white men, although there have been reports of cases in children as well. It should therefore be kept on the differential diagnosis when examining children with plaques that resemble GF. Patients with GF who complain of any symptoms of the upper respiratory tract (nasal obstruction, discharge, pain, epistaxis, or sinusitis) should be evaluated by an otolaryngologist to rule out the possibility of associated EAF.
There have also been reports of unusual presentations of GF. In one instance, an older woman with GF had multiple plaques on both cheeks and arms that resembled keloids. In another case report, a patient presented with disseminated GF involving the face, trunk, and proximal extremities.
What is the Evidence?
Burns, BV, Roberts, PF, De Carpentier, J, Zarod, AP. “Eosinophilic angiocentric fibrosis affecting the nasal cavity. A mucosal variant of the skin lesion granuloma faciale”. J Laryngol Otol. vol. 115. 2001. pp. 223-6. (A case report describing EAF in the nasal cavity. It also describes the similarity of EAF to GF and suggests that the two may be due to the same pathologic process.)
Thiyanaratnam, J, Doherty, SD, Krishnan, B, Hsu, S. “Granuloma faciale: case report and review”. Dermatol Online J. vol. 15. 2009. pp. 3(A case presentation and review of granuloma faciale with successful treatment reported)
Rossiello, L, Palla, M, Aiello, FS, Baroni, A, Satriano, RA. “Granuloma faciale with extrafacial lesions”. Skinmed. vol. 6. 2007. pp. 150-1. (A case report on granuloma faciale with extrafacial involvement, with some background review and treatment recommendations)
Nigar, E, Dhillon, R, Carr, E, Matin, RN. “Eosinophilic angiocentric fibrosis and extrafacial granuloma faciale”. Histopathology. vol. 51. 2007. pp. 729-31. (A review of EAF, a disease associated with granuloma faciale, with good descriptions of both diseases, clinically and histologically)
Ortonne, N, Wechsler, J, Bagot, M, Grosshans, E, Cribier, B. “Granuloma faciale: a clinicopathologic study of 66 patients”. J Am Acad Dermatol. vol. 53. 2005. pp. 1002-9. (An outstanding study of sixty-six patients, detailing the gross appearance, histological appearance, distribution, and pathologic features of GF)
LeBoit, PE. “Granuloma faciale: a diagnosis deserving of dignity”. Am J Dermatopathol. vol. 24. 2002. pp. 440-3. (An interesting article that discusses how physicians and clinicians find it difficult to diagnose GF. The author describes it as a distinct entity separate from erythema elevatum diutinum, and provides an overview of the disease.)
Tomson, N, Sterling, JC, Salvary, I. “Granuloma faciale treated successfully with topical tacrolimus”. Clin Exp Dermatol. vol. 34. 2009. pp. 424-5. (An excellent paper on the use of tacrolimus in the treatment of GF. It describes the successful outcomes of two patients and provides details of the treatment regimen.)
Panagiotopoulos, A, Anyfantakis, V, Rallis, E, Chasapi, V, Stavropoulos, P, Boubouka, C. “Assessment of the efficacy of cryosurgery in the treatment of granuloma faciale”. Br J Dermatol. vol. 154. 2006 Feb. pp. 357-60. (A paper detailing the successful treatment of GF with cryosurgery. Nine patients were treated by open-spray and contact cryo-probe, and no recurrence was noted after 24 months.)
Cheung, ST, Lanigan, SW. “Granuloma faciale treated with the pulsed-dye laser: a case series”. Clin Exp Dermatol. vol. 30. 2005. pp. 373-5. (A case series about the successful treatment of GF with pulsed dye laser. The settings and shortcomings of the treatment are detailed.)
Smoller, BR, Bortz, J. “Immunophenotypic analysis suggests that granuloma faciale is a gamma-interferon-mediated process”. J Cutan Pathol. vol. 20. 1993. pp. 442-6. (An excellent paper that studies the composition of the cells in GF with different immune markers. The pathogenesis of GF is postulated with some evidence.)
Welsh, JH, Schroeder, TL, Levy, ML. “Granuloma faciale in a child successfully treated with the pulsed dye laser”. J Am Acad Dermatol. vol. 41. 1999. pp. 351-3. (A case report describing the occurrence of GF in an 11-year-old child and the successful use of pulsed-dye laser in treating the condition.)
Verma, R, Das, AL, Vaishampayan, SS, Vaidya, S. “Keloidal granuloma faciale with extrafacial lesions”. Indian J Dermatol Venereol Leprol. vol. 71. 2005. pp. 345-7. (A case report of an unusual presentation of GF. A 52-year-old woman had multiple lesions on both cheeks and arms; these lesions had a keloidal appearance.)
Zargari, O. “Disseminated granuloma faciale”. Int J Dermatol. vol. 43. 2004. pp. 210-2. (This paper describes an unusual case of GF that was disseminated on the face, trunk, and proximal extremities.)
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