:: Volume 24, Issue 3 (7-2012) ::
J Iran Dent Assoc 2012, 24(3): 111-121 Back to browse issues page
Approach to Orofacial Granulomatosis and Review of Literature
Abbas Javadzade1, Ates sa Pakfetrat1, Farnaz Falaki2, Amir Seyyedi *3
1- Associate Professor, Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences. Mashhad, Iran
2- Assistant Professor, Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences. Mashhad, Iran
3- Assistant Professor, Department of Oral Medicine, School of Dentistry, Urmia University of Medical Sciences. Urmia, Iran , seyyedia871@mums.ac.ir
Abstract:   (8881 Views)


  Background and Aim : Orofacial granulomatosis (OFG) comprises a group of diseases characterized by non-caseating granulomatous inflammation affecting the soft tissues of the oral and maxillofacial region.

  Wiesenfeld introduced the term orofacial granulomatosis in 1985 for the first time. The precise cause of OFG is unknown however, some theories have been suggested including allergy, infection and genetic predisposition.

  The clinical presentation can be highly variable, making the diagnosis difficult to establish.

  The aim of this review was to define clinical features, differential diagnosis and treatment protocols of OFG .

  Materials and Methods : All English articles from 1950 to 2010 in Pubmed, InterScience, ScienceDirect, Google Scholar databases were searched using the keywords : orofacial granulomatosis, approach, and treatment. Persian articles were also selected from Iran Medex .

  Results and Conclusion : Because of the relatively nonspecific clinical findings associated with a variety of granulomatous diseases, the diagnosis of orofacial granulomatous often presents a dilemma for the clinician. The most common differential diagnosis includes Crohn's disease, sarcoidosis, and infection. However, a variety of other conditions may be associated with granuloma formation. Often an extensive clinical, microscopic, and laboratory evaluation may be required to reach to definite diagnosis and proper treatment .

Keywords: Orofacial granulomatosis, Approach, Treatment
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Type of Study: Orginal | Subject: Oral Medicine
1. Wiesenfeld D, Ferguson MM, Mitchell DN, MacDonald DG, Scully C, Cochran K, et al. Oro-facial granulomatosis – A clinical and pathological analysis. Q J Med. 1985 Jan;54(213):101-13.
2. Challacombe SJ. Oro-facial granulomatosis and oral crohns disease: Are they specific dis-eases and do they predict systemic Crohns dis-ease? Oral Dis. 1997 Sep;3(3):127-9.
3. Alioğlu Z, Caylan R, Adanir M, Ozmenoğlu M..Melkersson-Rosenthal syndrome: report of three cases. Neurol Sci. 2000 Feb;21(1):57-60.
4. Rosenthal C.Klinisch-erbbiologischer Beitrag zur Kon- stitutions-Patologie: Gemeinsames Aiftreten von (rezidivie- render familiarer) Fazialislahmung, angineurotschem Gesichtsodem und Lingua plicata in Arthris-musfamilien. Ztschr Neurol Psych 1931; 131:475–501.
5. Kuske H. Macrocheilia granulomatosa with recurrent right facial nerve paralysis (Melkers-son-Rosenthal synd.); cheilitis granulomatosa; macrocheilia with chronic recurrent erysipelas of the upper lip. Dermatologica. 1955 Mar-May; 110 (3-5):392-6.
6. Shengold MA, Sheingold H.Oral tuberculo-sis.Oral Surg Oral Med Oral Pathol. 1951 Feb;4 (2):239 .50.
7. Crohn BB, Ginsburg L, Oppenheimer GD. Regional ileitis 1932: A pathologic and clinical entity. Mt Sinai J Med. 2000 May;67(3):263-8.
8. Sanderson J, Nunes C, Escudier M,et al. Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease? Inflamm Bowel Dis. 2005 Sep;11(9):840-6.
9. Mignogna MD, Fedele S, Lo RL, Lo ML. The multiform and variable patterns of onset of oro-facial granulomatosis J Oral Pathol Med. 2003 Apr;32(4):200-5.
10. Odukoya O. Orofacial granulomatosis: re-port of two Nigerian cases. J Trop Med Hyg. 1994 Dec; 97(6):362-6.
11. Rogers RS III. Melkersson-Rosenthal syn-drome and orofacial granulomatosis. Dermatol Clin. 1996 Apr;14(2):371-9.
12. Sainsbury CP, Dodge JA, Walker DM, Al-dred MJ. Orofacial granulomatosis in child-hood. Br Dent J. 1987 Sep 5; 163(5):154-7.
13. Clayden AM, Bleys CM, Jones SF, Savage NW, Aldred MJ. Orofacial granulomatosis: A diagnostic problem for the unw-ary and a man-agement dilemma. Aust Dent J. 1997 Aug; 42(4):228-32.
14. Eveson JW. Granulomatous disorders of the oral mucosa. Semin Diagn Pathol. 1996 May; 13 (2):118-27.
15. Leão JC, Hodgson T, Scully C, Porter S. Review article: orofacial granulomatosis. Aliment Pharmacol Ther. 2004 Nov 15;20(10):1019-27
16. Daley T, Armstrong J. Oral manifestations of gastrointestinal diseases. Can J Gastroenterol. 2007 Apr;21(4):241-4.
17. Sciubba JJ, Said-AI-Naief N. Orofacial granulomatosis: Presentation, pathology and management of 13 casesJ Oral Pathol Med. 2003 Nov; 32(10):576-85.
18. Nevil B, Damm D, Allen C, Bouquot J.Oral and Maxillofacial Pathology. 3rd. ed. Philaadel-phia: W.B. Saunders; 2009;341-345.
19. Mignogna MD, Fedele S, Lo RL, Lo ML. Orofacial granulo-matosis with gingival onset. J Clin Periodontol. 2001 Jul;28(7):692-6.
20. Gottwald W. Melkersson-Rosenthal syn-drome: 2. Diagnosis, differential diagnosis, course, prognosis, neuropathology, therapy. Fortschr Med. 1981 Mar 12;99(10):326-30.
21. James J, Ferguson MM.Orofacial granulomatosis presenting clinically as tuberculosis of cervical lymph nodes. Br Dent J. 1986 Jul 5; 161(1):17-9.
22. Loftus EV Jr. Clinical epidemiology of in-flammatory bowel disease: incidence, preva-lence, and environmental influences. Gastroen-terology. 2004 May;126(6):1504-17.
23. Oliver AJ, Rich AM, Reade PC, Varigos GA, Radden BG. Monosodium glutamate-related orofacial granulomatosis. Review and case re-port. Oral Surg Oral Med Oral Pathol. 1991 May; 71 (5):560-4.
24. Taibjee SM, Prais L, Foulds IS. Orofacial granulomatosis worsened by chocolate: results of patch testing to ingredients of Cadbury’s chocolate. Br J Dermatol. 2004 Mar;150(3):595.
25. Lazarov A, Kidron D, Tulchinsky Z, Min-kow B. Contact orofacial granulomatosis caused by delayed hypersensitivity to gold and mercu-ry. J Am Acad Dermatol. 2003 Dec;49(6):1117-20.
26. Guttman-Yassky E, Weltfriend S, Bergman R. Resolution of orofacial granulomatosis with amalgam removal. J Eur Acad Dermatol Vene-reol. 2003 May;17(3):344-7.
27. Riggio MP, Gibson J, Lennon A, Wray D, MacDonald DG. Search for Mycobacterium paratuberculosis DNA in orofacial granulo-matosis and oral Crohn’s disease tissue by pol-ymerase chain reaction. Gut. 1997 Nov; 41(5):646-50.
28. Meisel-Stosiek M, Hornstein OP, Stosiek N.Family study on Melkersson-Rosenthal syn-drome. Some hereditary aspects of the disease and review of literature.Acta Derm Venereol. 1990; 70 (3):221-6.
29. Van der Waal RIF, Schulten EAJM, Van de Scheur MR, et al.Cheilitis granulomatosa.J Eur Acad Dermatol Venereol. 2001 Nov;15(6):519-23.
30. Satsangi J, Jewell DP, Rosenberg WMC, Bell JI. Genetics of inflammatory bowel disease. Gut. 1994 May; 35(5):696-700.
31. Gibson J, Wray D. Human leucocyte antigen typing in` orofacial granulomatosis. Br J Derma-tol. 2000 Nov; 143(5):1119-21.
32. James J, Patton DW, Lews CJ, Kirkwood MM, Ferguson MM.Orofacial granulomatosis and clinical atopy. J Oral Med. 1986 Jan-Mar; 41 (1):29-30.
33. Armstrong DK, Biagioni P, Lamey PJ, Bur-rows D. Contact hypersensitivity in patients with orofacial gra- nulomatosis. Am J Contact Dermat. 1997 Mar;8(1):35-8.
34. Sweatman MC, Tasker R, Warner JO, Fergu-son MM, MitchelDN. Orofacialgranulomatosis. Response to elemental diet and provocation by food additives. Clin Allergy. 1986 Jul;16(4):331-8.
35. Sciubba J, Said - Al - Naief N.Orofacial granu-lomatosis: Presentation, pathology and man-agement of 13 cases. J Oral Pathol Med. 2003 Nov;32(10):576-85.
36. Patton DW, Fergusion MM, Forsyth A, James J.Orofa- cial granulomatosis; a possible allergic bias. Br J Oral Maxillofac Surg. 1985 Aug; 23(4): 235-42.
37. Levy FS, Bircher AJ, Buchner SA. Delayed-type hyper-sensitivity to cow’s milk protein in Melkersson-Rosenthal syndrome: Coincidence or pathogenic role? Dermatology 1996;192(2):99-102.
38. Pryce DW, King CM. Orofacial granulo-matosis associated with delayed hypersensitivity to cobalt. Clin Exp Dermatol. 1990 Sep;15(5):384-6.
39. Gibson J, Wray D, Bagg J. Oral staphylo-coccal mucositis: A new clinical entity in orofa-cial granulomatosis and Crohn's disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Feb;89(2):171-6.
40. Apaydin R, Bahadir S, Kakklikkaya N, Bi-len N, Bay- ramguler D. Possible role of Myco-bacterium tuberculosis complex in Melkersson Rosenthal syndrome demonstrated with Gen-probe ampli.ed Mycobacterium tuberculosis direct test. Australas J Dermatol. 2004 May; 45(2):94-9.
41. Ivanyl L, Kirby A, Zakrzewska JM. Anti-bodies to Mycobacterial stress protein in pa-tients with orofacial granulomatosis. J Oral Pathol Med. 1993 Aug;22(7):320-2.
42. Savage NW, Barnard K, Shirlaw PJ, Rahman D, Mistry M, Escudier MP, et al. Serum and sal-ivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease. Clin Exp Immunol. 2004 Mar;135(3):483-9.
43. Muellegger RR,Weger W, Zoechling N, et al. Granulo-matous cheilitis and Borrelia burgdor-feri: polymerase chain reaction and serologic studies in a retrospective case series of 12 pa-tients. Arch Dermatol. 2000 Dec; 136(12):1502-6.
44. Liu HG. Spirochetes in the cheilitis granu-lomatosa and sarcoidosis. Zhonghua Yi Xue Za Zhi.1993Mar;73(3):142-4,189-90.
45. Liu HG, Zheng LF, Xiao XZ. Relationship between Melkersson-Rosenthal syndrome and Spirochetes infection. Zhonghua Yi Xue Za Zhi. 1994 Feb;74(2):92-3, 127.
46. Liu H, Zheng L, Liu H. Spirochetes. The possible etiological factor of the cheilitis granu-lomatosa. Chin Med Sci J. 2001 Mar; 16(1): 52-5.
47. Freysdottir J, Zhang S, Tilakaratne WM, For-tune F. Oral biopsies from patients with orofa-cial granulomatosis with histology resembling Crohn’s disease have a prominent Th1 envi-ronment. Inflamm Bowel Dis. 2007 Apr; 1(4):439-45.
48. Facchetti F, Signorini S, Majorana A, Mangannoni MA, Sapelli P, Imberti L. Non-specific influx of T-cell receptor alpha/beta and gamma/delta lymphocytes in mucosal biopsies from a patient with orofacial granulomatosis. J Oral Pathol Med. 2000 Nov;29(10):519-22.
49. Bishop RP, Brewster AC, Antonioli DA. Crohn’s disease of the mouth. Gastroenterolo-gy. 1972 Feb;62(2):302-6.
50. Li MC, Chou G, Chen JT, Wong YK, Ho WL. Amyloidosis of medium-sized arteries pre-senting as perioral mass: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Apr; 95(4): 463-6.
51. Fujimura T, Aiba S, Suetake T, Tagami H. Erythematous swelling of the lip associated with Sjogren’s syndrome and mimicking cheilitis granulomatosa. J Dermatol. 2001 Jan;28(1):47-9.
52. Hodgson TA, Haricharan AK, Barrett AW, Porter SR. Microcystic adnexal carcinoma: an unusual cause of swell-ing and paraesthesia of the lower lip. Oral Oncol. 2003 Feb;39(2):195-8.
53. High CL, Houston GD. Recurring anterior facial swelling. Compend Contin Educ Dent. 2001 Dec;22(12):1066-8, 1070, 1072.
54. Takada K, Ina Y, Noda M, Sato T, Yama-moto M, Morishita M. The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis. J Clin Epidemiol. 1993 Apr; 46(4): 359-66.
55. Krysl J, Korzeniewska-Kosela M, Muller NL, FitzGerald JM. Radiologic features of pul-monary tuberculosis: an assessment of 188 cas-es. Can Assoc Radiol J. 1994 Apr;45(2):101-7.
56. Alien R, Mendelsohn FA, Csicsmann J, Weller RF, Hurley TH, Doyle AE. A clinical evaluation of serum angiotensin con-verting enzyme in sarcoidosis. Aust N Z J Med. 1980 Oct; 10(5):496-501.
57. Khan K, Schwarzenberg SJ, Sharp H, Greenwood D, Weisdorf-Schindele S. Role of serology and routine laboratory tests in child-hood inflammatory bowel disease. Inflamm Bowel Dis. 2002 Sep; 8(5):325-9.
58. Dupuy A,Cosnes J,Revuz J,Delchier JC,Gendre JP, Cosnes A. Oral Crohn disease: Clinical characteristics and long-term follow-up of 9 cases.Arch Dermatol. 1999 Apr;135(4):439-42.
59. Rogers RS III (2000). Granulomatous cheilitis, Melkersson. Rosenthal syndrome, and orofacial granulomatosis. Arch Dermatol. 2000 Dec; 136 (12):1557-8.
60. Reed BE, Barrett AP, Katelaris C, Bilous M. Orofacial sensi-tivity reactions and the role of dietary components. Case reports. Aust Dent J. 1993 Aug;38(4):287-91.
61. Van der Waal RL, Schulten EA, Van der Meij EH, Van de Scheur MR, Starink TM, Van der Waal I. Cheilitis granulo-matosa: Overview of 13 patients with long-term follow-up-results of managementInt. J Dermatol. 2002 Apr;41(4):225-9.
62. Mignogna MD, Fedele S, Lo Russo L, Ada-mo D, Satriano RA (2004).E. Ectiveness of small-volume, intralesional, delayed-release tri-amcinolone injections in orofacial granulomato-sis:a pilot study. Int J Dermatol. 2002 Apr; 41(4):225-9.
63. Sussman GL, Yang WH, Steinberg S. Melk-ersson-Rosenthal syndrome: clinical, patholog-ic, and therapeutic considera-tions. Ann Aller-gy. 1992 Sep;69(3):187-94.
64. Hegarty A, Hodgson T, Porter S. Thalido-mide for the treat-ment of recalcitrant oral Crohn’s disease and orofacial gra-nulomatosis. Oral Surg Oral Med Oral Pathol Oral Radiol En-dod. 2003 May; 95 (5):576-85.
65. Casson DH, Eltumi M, Tomlin S, Walker-Smith JA, Murch SH. Topical tacrolimus may be e. ective in the treatment of oral and perineal Crohn ’s disease.Gut. 2000 Sep;47(3):436-40.
66. Mahadevan U, Sandborn WJ. Infliximab for the treatment of orofacial Crohn’s disease. In-flamm Bowel Dis. 2001 Feb;7(1):38-42.
67. Targan SR, Hanauer SB, Van Deventer SJ, Mayer L, Present DH, Braakman T, et al. A short-term study of chimeric monoclonal anti-body cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997 Oct 9;337(15):1029-35.
68. Gaya DR, Aitken S, Fennell J, Satsangi J, Shand AG. Anti-TNF-alpha therapy for orofa-cial granulomatosis: Proceed with caution. Gut. 2006 Oct;55(10):1524-5.
69. Allen CM, Camisa C, Hamzeh S, Stephens L. Cheilitis granulomatosa: Report of six cases and review of the literature. J Am Acad Derma-tol. 1990 Sep;23(3 Pt 1):444-50.
70. Olivier V, Lacour JP, Castanet J, Perrin C, Ortonne JP. Cheilitis granulomatosa in a child. Arch Pediatr. 2000 Mar; 7(3):274-7.
71. Kauzman A, Quesnel-Mercier A, Lalonde B .Orofacial Granulomatosis: 2 Case Reportsand Literature Review. J Can Dent Assoc. 2006 May; 72 (4):325-9.

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Volume 24, Issue 3 (7-2012) Back to browse issues page