Continuing Education Activity

Granuloma faciale (GF) is a rare, benign, inflammatory skin disease, usually presenting as isolated, well-defined reddish-brown to violaceous asymptomatic papules, nodules or plaques showing follicular accentuation and telangiectasia. Granuloma faciale is most commonly seen in middle-aged white males between their second and seventh decades of life, although it has also been reported in childhood. It usually appears as a single lesion on the face, but can also present with multiple lesions on the face or elsewhere. Extrafacial GF locations may include the scalp, trunk, nasal cavity or extremities. The facial lesions most commonly present on the forehead, nose, or cheeks. This activity reviews the evaluation of a patient with granuloma faciale and the role of the interprofessional team in the management of this condition.

Objectives:

• Describe the presentation of granuloma faciale.
• Explain when granuloma faciale should be considered on differential diagnosis.
• Outline the treatment of granuloma faciale.
• Explore modalities to improve care coordination among interprofessional team members in order to optimize outcomes for patients affected by granuloma faciale.

Introduction

Granuloma faciale (GF) is a rare, benign, inflammatory skin disease, usually presenting as isolated, well-defined reddish-brown to violaceous asymptomatic papules, nodules or plaques showing follicular accentuation and telangiectasia. It was first described as 'eosinophilic granuloma' in 1945 by Wigley JE.[1] Granuloma faciale is most commonly seen in middle-aged white males (between the second and seventh decades of life), but it has been reported in childhood too.[2][3][4] It usually appears as a single lesion on the face, but occurrence can be as multiple lesions and/or extrafacial. Extrafacial GF localizations are possible, including localization on the scalp, trunk, nasal cavity or extremities. The facial lesions most commonly present on the forehead, nose, or cheeks.[3][5]

Etiology

The etiology of granuloma faciale is unknown, but because of the localization on mainly sun-exposed areas of the body, the thinking is that the condition is related to actinic damage. Other possible etiologies include allergy and trauma.[6] Radiation therapy is considered to be another potential trigger.[7]

Epidemiology

Granuloma faciale is a relatively rare condition that occurs mainly in adult people from both sexes with a slight predilection in men. All races can be affected, but GF most commonly presents in whites. The mean age of onset is around 52 years.[8][9]

Pathophysiology

The pathogenesis of GF is not well established. It is considered to be a variant of chronic cutaneous vasculitis possibly secondary to an underlying localized Arthus phenomenon.[10]

Histopathology

Specific histopathologic features have do not yet exist for granuloma faciale. The most frequent histologic features reported are the presence of Grenz zone, infiltration of neutrophils and telangiectasia.[3]

The inflammatory infiltrates in the dermis are usually separated from the overlying epidermis by a narrow Grenz zone of the uninvolved dermis. Dilated follicular ostia and/or follicular plugs are frequently observed.[3][8][2]

The inflammatory infiltrates in the dermis are mostly perivascular and consist mainly of neutrophils, lymphocytes, and plasma cells. Eosinophils are also frequently observed.[3][8][2]  

Vascular changes are frequent presentations, and they consist mainly of perivascular infiltrates which could penetrate the vascular wall and causing leukocytoclasis. However necrotizing vasculitis is very rare. Moreover, the presence of hemosiderin and red blood cell deposits are consistent with vascular injury.[3][2] 

Direct immunofluorescence is not positive in all cases and not pathognomonic for granuloma faciale. Positive findings seen on direct immunofluorescence include granular deposits of IgG with less intense deposits of IgM, and in some cases, IgA, C3, and C1q localized in the perivascular areas or the basement membrane zone.[10][3]

History and Physical

Granuloma faciale typically presents as a chronic, progressive, asymptomatic, isolated, well-defined reddish-brown to a violaceous asymptomatic papule, nodule or plaques showing follicular accentuation and telangiectasia. The most common sites are the face and other sun-exposed areas. Dermoscopy is a useful tool for the clinical evaluation of GF. Dermoscopy typically reflects the clinical and histological features. The most common dermoscopic features include: linear, arborizing vessels, dilated follicular openings and brown dots/ globules. The brown dots/ globules are considered to reflect hemosiderin deposition.[11]

Evaluation

Granuloma faciale has a progressive, chronic course with recurrent acute phases, rather than having a distinct acute and chronic phase. It is therefore difficult to comment on the chronicity based on histopathology as cases might show overlapping features of acute and chronic inflammation.[3] Laboratory evaluation is normal except for mild blood eosinophilia.[8] Granuloma faciale is a benign condition, but spontaneous healing is rare, so most cases require therapeutic intervention, but presently available treatment options associated with significant chances of recurrence.[12][13]

Treatment / Management

The treatment of granuloma faciale include is difficult, with variable clinical outcomes. Treatment modalities reported to be useful in granuloma faciale include:

• Topical treatment, which is considered as first-line therapy, and it includes topical corticosteroids or tacrolimus - topical dapsone is another option in GF
• Intralesional corticosteroids have been reported to be  effective in some cases
• Systemic treatment, including systemic corticosteroids and dapsone
• Phototherapy including psoralens plus ultraviolet A (PUVA)
• Other therapeutic modalities including lasers, cryotherapy, and surgical excision

Differential Diagnosis

Several cutaneous conditions present with an appearance similar to granuloma faciale include. Clinical differential diagnosis includes sarcoidosis, discoid lupus erythematosus, rosacea, mycobacterial infections cutaneous deep fungal infections, cutaneous lymphoma, and basal cell carcinoma.[2][5][3][14]

Erythema elevatum diutinum (EED) is a histopathological differential diagnosis for granuloma faciale include and can show similar histological features like fibrosing vasculitis. It is possible that both EED and GF have a common underlying pathogenic mechanism. The main difference between these two entities is clinical, as EED usually presents as multiple lesions on the extensor surfaces of the joints, and GF usually a single facial lesion. The diagnosis is more challenging when EED presents on the face, or in the case of extra facial localization with GF.[5][8][15] However, a high number of eosinophils strongly favors the diagnosis of GF. On the other hand, the granulomatous nodules in the histopathologic examination are present in some cases of EED.[15] Additionally, EED commonly correlates with some underlying disease, mainly hematological abnormalities, autoimmune conditions, HIV infections, other infectious diseases, and insect bites. However, granuloma faciale include is rarely associated with other systemic diseases.[15]

Treatment Planning

Topical treatments are considered to be first-line therapy in granuloma faciale include:

• Calcineurin inhibitors especially tacrolimus are considered to be the first line topical treatment for GF. Topical calcineurin inhibitors decrease T-cell activation and also decrease the upregulation of interleukin-2[5]; Tacrolimus 0.1% ointment, applied twice daily, seems to be the most effective primary treatment option.[16][17][18][19][20] However, lesion clearance might take several months, and healing may require up to 2 to 6 months of treatment in most cases.[21][22][23][24]
• Corticosteroids as topical or intralesional therapy have been reported to be effective in granuloma faciale include with variable results. Intralesional corticosteroids can are an option in combination with cryotherapy. The most common dose of intralesional corticosteroids used is triamcinolone acetonide 5 to 20 mg/ml once weekly or once monthly infiltrations.[25][26][27][28][29][30]
• A case report discussed the efficacy of topical dapsone 5% gel with a good outcome.[31]
• Intralesional rituximab was tried in three cases at a dose of 10 mg/ml once monthly, with relatively good results.[32] 

Systemic treatments:

• Dapsone at dose 50 to 150 mg/day has demonstrated effectiveness as a treatment option for granuloma faciale.[33][34][35] Dapsone has an anti-inflammatory, antimicrobial and antiprotozoal effects. The mechanism of action is not well understood, and the anti-inflammatory effect could be related to several mechanisms including inhibition of prostaglandin synthesis and production, and prevention of the extravasation of neutrophils to the lesional site.[36][37]
• Systemic corticosteroids have been reported to be effective but with only partial improvement in most cases.[38][39]
• Clofazimine is an anti-leprosy treatment with anti-inflammatory and anti-proliferative effects for lymphocytes and carcinoma cells. It has received minimal discussion as a treatment of GF at a dose of 300 mg/day with good effect after 3 to 5 months of treatment.[40][41][33]

Surgical and other therapies:

• Cryotherapy with liquid nitrogen as a single treatment seems to be a good choice for treating GF.[42]
• Various types of laser are discussed in medical literature with the variable outcomes depending on the lesion, type of laser used, and the operating physician as well, and this includes: 

1. Pulsed dye laser (PDL). It targets oxyhemoglobin in blood vessels. Good cosmetic outcomes have been reported, especially for superficial lesions. For the maximal possible benefit, several sittings may be necessary. The time interval between laser treatments is about 2 to 4 months. PDL correlates with a lower risk of scarring as compared to other types of laser, and its main side effects are pain during the procedure and bruising after the procedure.[43][44][45][46]
2. Potassium-titanyl-phosphate (KTP) - 532-nm has been reported to be effective with good results reported after 5 to 10 days of daily treatment, without significant scarring.[12]
3. Carbon-dioxide (CO2) laser.[47][48][30]
4. Argon laser at 480 to 520 nm. This type of laser has a more selective effect on oxyhemoglobin than CO2 laser, but it causes further non-specific tissue destruction due to diffusion of the created heat over a large area.[49][45]

• Phototherapy including topical psoralen-ultraviolet A (PUVA).[50]
• Surgical excision with and without grafting. Dermabrasion is a therapeutic choice as well.[51][12]

Enhancing Healthcare Team Outcomes

Primary care providers and nurse practitioners who see facial lesions should refer these patients to the dermatologist for definitive workup. It is essential to evaluate granuloma faciale along with the dermatopathologist to ensure the accuracy of diagnosis because of the large number of clinical and histological differentials. an interprofessional team approach that includes physicians, nurse practitioners, PAs, and pharmacists gives the best opportunity for successful case management and patient care.

Surgical treatment, especially for facial lesions, needs to be planned in collaboration with a plastic surgeon.