Tools
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
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
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:
- 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]
- 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]
- Carbon-dioxide (CO2) laser.[47][48][30]
- 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]
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.
References
Wigley JE. Eosinophilic Granuloma. ? Sarcoid of Boeck. Proceedings of the Royal Society of Medicine. 1945 Jan:38(3):125-6 [PubMed PMID: 19992999]
Oliveira CC, Ianhez PE, Marques SA, Marques ME. Granuloma faciale: clinical, morphological and immunohistochemical aspects in a series of 10 patients. Anais brasileiros de dermatologia. 2016 Nov-Dec:91(6):803-807. doi: 10.1590/abd1806-4841.20164628. Epub [PubMed PMID: 28099604]
Ortonne N, Wechsler J, Bagot M, Grosshans E, Cribier B. Granuloma faciale: a clinicopathologic study of 66 patients. Journal of the American Academy of Dermatology. 2005 Dec:53(6):1002-9 [PubMed PMID: 16310061]
Level 2 (mid-level) evidenceDeen J, Moloney TP, Muir J. Extrafacial Granuloma Faciale: A Case Report and Brief Review. Case reports in dermatology. 2017 May-Aug:9(2):79-85. doi: 10.1159/000477960. Epub 2017 Jul 13 [PubMed PMID: 28868005]
Level 3 (low-level) evidenceLindhaus C, Elsner P. Granuloma Faciale Treatment: A Systematic Review. Acta dermato-venereologica. 2018 Jan 12:98(1):14-18. doi: 10.2340/00015555-2784. Epub [PubMed PMID: 28880343]
Level 1 (high-level) evidenceNigar E, Dhillon R, Carr E, Matin RN. Eosinophilic angiocentric fibrosis and extrafacial granuloma faciale. Histopathology. 2007 Nov:51(5):729-31 [PubMed PMID: 17927606]
Level 3 (low-level) evidenceGoldner R, Sina B. Granuloma faciale: the role of dapsone and prior irradiation on the cause of the disease. Cutis. 1984 May:33(5):478-9, 482 [PubMed PMID: 6478871]
Level 3 (low-level) evidenceMarcoval J, Moreno A, Peyr J. Granuloma faciale: a clinicopathological study of 11 cases. Journal of the American Academy of Dermatology. 2004 Aug:51(2):269-73 [PubMed PMID: 15280847]
Level 3 (low-level) evidenceRadin DA, Mehregan DR. Granuloma faciale: distribution of the lesions and review of the literature. Cutis. 2003 Sep:72(3):213-9; quiz 208 [PubMed PMID: 14533833]
Barnadas MA, Curell R, Alomar A. Direct immunofluorescence in granuloma faciale: a case report and review of literature. Journal of cutaneous pathology. 2006 Jul:33(7):508-11 [PubMed PMID: 16872475]
Level 3 (low-level) evidenceLallas A, Sidiropoulos T, Lefaki I, Tzellos T, Sotiriou E, Apalla Z. Photoletter to the editor: Dermoscopy of granuloma faciale. Journal of dermatological case reports. 2012 Jun 30:6(2):59-60. doi: 10.3315/jdcr.2012.1101. Epub [PubMed PMID: 22826723]
Level 3 (low-level) evidenceLudwig E, Allam JP, Bieber T, Novak N. New treatment modalities for granuloma faciale. The British journal of dermatology. 2003 Sep:149(3):634-7 [PubMed PMID: 14511001]
Level 3 (low-level) evidenceTomson N,Sterling JC,Salvary I, Granuloma faciale treated successfully with topical tacrolimus. Clinical and experimental dermatology. 2009 Apr; [PubMed PMID: 19175788]
Level 3 (low-level) evidenceFrankel DH, Soltani K, Medenica MM, Rippon JW. Tinea of the face caused by Trichophyton rubrum with histologic changes of granuloma faciale. Journal of the American Academy of Dermatology. 1988 Feb:18(2 Pt 2):403-6 [PubMed PMID: 3343409]
Level 3 (low-level) evidenceZiemer M, Koehler MJ, Weyers W. Erythema elevatum diutinum - a chronic leukocytoclastic vasculitis microscopically indistinguishable from granuloma faciale? Journal of cutaneous pathology. 2011 Nov:38(11):876-83. doi: 10.1111/j.1600-0560.2011.01760.x. Epub 2011 Aug 23 [PubMed PMID: 21883365]
Lima RS, Maquiné GÁ, Silva Junior RC, Schettini AP, Santos M. Granuloma faciale: a good therapeutic response with the use of topical tacrolimus. Anais brasileiros de dermatologia. 2015 Sep-Oct:90(5):735-7. doi: 10.1590/abd1806-4841.20153339. Epub [PubMed PMID: 26560220]
Cecchi R, Pavesi M, Bartoli L, Brunetti L. Topical tacrolimus in the treatment of granuloma faciale. International journal of dermatology. 2010 Dec:49(12):1463-5. doi: 10.1111/j.1365-4632.2009.04317.x. Epub [PubMed PMID: 21091691]
Level 3 (low-level) evidencePérez-Robayna N, Rodríguez-García C, González-Hernández S, Sánchez R, Guimerá F, Sáez M. Successful response to topical tacrolimus for a granuloma faciale in an elderly patient. Dermatology (Basel, Switzerland). 2009:219(4):359-60. doi: 10.1159/000243806. Epub 2009 Oct 1 [PubMed PMID: 19797891]
Level 3 (low-level) evidenceMitchell D. Successful treatment of granuloma faciale with tacrolimus. Dermatology online journal. 2004 Oct 15:10(2):23 [PubMed PMID: 15530313]
Level 3 (low-level) evidenceEetam I,Ertekin B,Unal I,Alper S, Granuloma faciale: Is it a new indication for pimecrolimus? A case report. The Journal of dermatological treatment. 2006; [PubMed PMID: 16971320]
Level 3 (low-level) evidenceMarcoval J, Moreno A, Bordas X, Peyrí J. Granuloma faciale: treatment with topical tacrolimus. Journal of the American Academy of Dermatology. 2006 Nov:55(5 Suppl):S110-1 [PubMed PMID: 17052523]
Level 3 (low-level) evidenceJedlicková H, Feit J, Semrádová V. Granuloma faciale successfully treated with topical tacrolimus: a case report. Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 2008 Mar:17(1):34-6 [PubMed PMID: 18454269]
Level 3 (low-level) evidencePatterson C, Coutts I. Granuloma faciale successfully treated with topical tacrolimus. The Australasian journal of dermatology. 2009 Aug:50(3):217-9. doi: 10.1111/j.1440-0960.2009.00543.x. Epub [PubMed PMID: 19659988]
Level 3 (low-level) evidenceDourmishev L, Ouzounova-Raykova V, Broshtilova V, Miteva L. Granuloma faciale effectively treated with topical pimecrolimus. Acta dermatovenerologica Croatica : ADC. 2014:22(4):305-7 [PubMed PMID: 25580794]
Level 3 (low-level) evidenceDowlati B, Firooz A, Dowlati Y. Granuloma faciale: successful treatment of nine cases with a combination of cryotherapy and intralesional corticosteroid injection. International journal of dermatology. 1997 Jul:36(7):548-51 [PubMed PMID: 9268759]
Level 3 (low-level) evidenceZargari O. Disseminated granuloma faciale. International journal of dermatology. 2004 Mar:43(3):210-2 [PubMed PMID: 15009395]
Level 3 (low-level) evidenceVerma R, Das AL, Vaishampayan SS, Vaidya S. Keloidal granuloma faciale with extrafacial lesions. Indian journal of dermatology, venereology and leprology. 2005 Sep-Oct:71(5):345-7 [PubMed PMID: 16394461]
Level 3 (low-level) evidenceMashood AA, Simeen-ber-Rahman. Granuloma faciale -- an unusual presentation. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2006 Apr:16(4):296-7 [PubMed PMID: 16624198]
Level 3 (low-level) evidenceDe D, Kanwar AJ, Radotra BD, Gupta S. Extrafacial granuloma faciale: report of a case. Journal of the European Academy of Dermatology and Venereology : JEADV. 2007 Oct:21(9):1284-6 [PubMed PMID: 17894740]
Level 3 (low-level) evidenceBakkour W, Madan V. Rhinophyma-like granuloma faciale successfully treated with carbon dioxide laser. The British journal of dermatology. 2014 Feb:170(2):474-5. doi: 10.1111/bjd.12649. Epub [PubMed PMID: 24111815]
Level 3 (low-level) evidenceBabalola O, Zhang J, Kristjansson A, Whitaker-Worth D, McCusker M. Granuloma faciale treated with topical dapsone: a case report. Dermatology online journal. 2014 Aug 17:20(8):. pii: 13030/qt9q7520rx. Epub 2014 Aug 17 [PubMed PMID: 25148282]
Level 3 (low-level) evidenceMorgado-Carrasco D, Giavedoni P, Mascaró JM Jr, Iranzo P. Assessment of Treatment of Refractory Granuloma Faciale With Intralesional Rituximab. JAMA dermatology. 2018 Nov 1:154(11):1312-1315. doi: 10.1001/jamadermatol.2018.2681. Epub [PubMed PMID: 30193300]
Holme SA, Laidler P, Holt PJ. Concurrent granuloma faciale and eosinophilic angiocentric fibrosis. The British journal of dermatology. 2005 Oct:153(4):851-3 [PubMed PMID: 16181479]
Level 3 (low-level) evidenceGupta L, Naik H, Kumar NM, Kar HK. Granuloma faciale with extrafacial involvement and response to tacrolimus. Journal of cutaneous and aesthetic surgery. 2012 Apr:5(2):150-2. doi: 10.4103/0974-2077.99463. Epub [PubMed PMID: 23060713]
Level 3 (low-level) evidenceFumo G, Patta F, Milo C, Pilloni L, Atzori L. A nose for trouble. Diagnosis: Granuloma faciale. Indian journal of dermatology, venereology and leprology. 2015 Jan-Feb:81(1):93-4. doi: 10.4103/0378-6323.148604. Epub [PubMed PMID: 25566920]
Level 3 (low-level) evidenceZampeli E, Moutsopoulos HM. Dapsone: an old drug effective for subacute cutaneous lupus erythematosus. Rheumatology (Oxford, England). 2019 May 1:58(5):920-921. doi: 10.1093/rheumatology/key434. Epub [PubMed PMID: 30615176]
Pfeiffer C, Wozel G. Dapsone and sulfones in dermatology: overview and update. Journal of the American Academy of Dermatology. 2003 Feb:48(2):308-9 [PubMed PMID: 12582416]
Level 3 (low-level) evidenceYuan C, Bu W, Chen X, Gu H. A case of granuloma faciale successfully treated with oral prednisone, tranilast and thalidomide. Postepy dermatologii i alergologii. 2018 Feb:35(1):109-112. doi: 10.5114/ada.2018.73170. Epub 2018 Feb 20 [PubMed PMID: 29599681]
Level 3 (low-level) evidenceSand FL, Thomsen SF. Off-label use of TNF-alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients. Dermatologic therapy. 2015 May-Jun:28(3):158-65. doi: 10.1111/dth.12222. Epub 2015 Mar 3 [PubMed PMID: 25731720]
Level 2 (mid-level) evidenceWollina U, Karte K, Geyer A, Stuhlert A, Bocker T. Clofazimine in inflammatory facial dermatosis--granuloma faciale and lipogranulomatosis subcutanea (Rothmann-Makai). Acta dermato-venereologica. 1996 Jan:76(1):77-9 [PubMed PMID: 8721503]
Level 3 (low-level) evidenceGómez-de la Fuente E, del Rio R, Rodriguez M, Guerra A, Rodriguez-Peralto JL, Iglesias L. Granuloma faciale mimicking rhinophyma: response to clofazimine. Acta dermato-venereologica. 2000 Mar-Apr:80(2):144 [PubMed PMID: 10877139]
Level 3 (low-level) evidencePanagiotopoulos A, Anyfantakis V, Rallis E, Chasapi V, Stavropoulos P, Boubouka C, Katsambas A. Assessment of the efficacy of cryosurgery in the treatment of granuloma faciale. The British journal of dermatology. 2006 Feb:154(2):357-60 [PubMed PMID: 16433810]
Fikrle T, Pizinger K. Granuloma Faciale treated with 595-nm pulsed dye laser. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2011 Jan:37(1):102-4. doi: 10.1111/j.1524-4725.2010.01823.x. Epub 2010 Nov 11 [PubMed PMID: 21070474]
Level 3 (low-level) evidenceHruza GJ, Ammirati CT. Granuloma faciale treated with 595-nm pulsed dye laser. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2011 Jul:37(7):1060-1. doi: 10.1111/j.1524-4725.2011.02035.x. Epub [PubMed PMID: 21711410]
Level 3 (low-level) evidenceCheung ST, Lanigan SW. Granuloma faciale treated with the pulsed-dye laser: a case series. Clinical and experimental dermatology. 2005 Jul:30(4):373-5 [PubMed PMID: 15953073]
Level 3 (low-level) evidenceErceg A, de Jong EM, van de Kerkhof PC, Seyger MM. The efficacy of pulsed dye laser treatment for inflammatory skin diseases: a systematic review. Journal of the American Academy of Dermatology. 2013 Oct:69(4):609-615.e8. doi: 10.1016/j.jaad.2013.03.029. Epub 2013 May 24 [PubMed PMID: 23711766]
Level 1 (high-level) evidenceChung WK, Park GH, Kim CH, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK. Keloidal granuloma faciale after CO2 laser treatment for melanocytic naevus. Journal of the European Academy of Dermatology and Venereology : JEADV. 2009 May:23(5):611-2 [PubMed PMID: 19415815]
Level 3 (low-level) evidenceWheeland RG, Ashley JR, Smith DA, Ellis DL, Wheeland DN. Carbon dioxide laser treatment of granuloma faciale. The Journal of dermatologic surgery and oncology. 1984 Sep:10(9):730-3 [PubMed PMID: 6434613]
Level 3 (low-level) evidenceApfelberg DB, Druker D, Maser MR, Lash H, Spence B Jr, Deneau D. Granuloma faciale. Treatment with the argon laser. Archives of dermatology. 1983 Jul:119(7):573-6 [PubMed PMID: 6859900]
Level 3 (low-level) evidenceHudson LD. Granuloma faciale: treatment with topical psoralen and UVA. Journal of the American Academy of Dermatology. 1983 Apr:8(4):559 [PubMed PMID: 6853786]
Level 3 (low-level) evidenceBergfeld WF, Scholes HT, Roenigk HH Jr. Granuloma faciale--treatment by dermabrasion. Report of a case. Cleveland Clinic quarterly. 1970 Oct:37(4):215-8 [PubMed PMID: 5520807]
Level 3 (low-level) evidence