Cheilitis Granulomatosa

  • Author: Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC); Chief Editor: Dirk M Elston, MD  more...
Updated: Feb 09, 2016


Cheilitis granulomatosa (or granulomatous cheilitis) is typically a chronic swelling of the lip due to granulomatous inflammation. Miescher cheilitis is the term used when the granulomatous changes are confined to the lip. Miescher cheilitis is generally regarded as a monosymptomatic form of the Melkersson-Rosenthal syndrome, although the possibility remains that these may be 2 separate diseases. (See the image below.)

Labial swelling and angular cheilitis. Labial swelling and angular cheilitis.

Melkersson-Rosenthal syndrome is the term used when the cheilitis occurs with facial palsy and plicated (fissured) tongue; this syndrome is occasionally a manifestation of Crohn disease[1, 2, 3, 4, 5, 6] or orofacial granulomatosis (OFG). The latter term is used when there is no detectable evidence of Crohn disease, but some patients progress to manifest overt Crohn disease. Other etiologies include sarcoidosis, tuberculosis, leprosy, histoplasmosis, foreign body reactions, and granulomatosis with polyangiitis.[7]  Thus, the terminology can be confusing.

Granulomatous cheilitis is a rare condition, although its actual frequency is unknown. Onset of granulomatous cheilitis usually is in young adult life. Swelling is typically chronic. Morbidity related to the disease depends also on whether an underlying organic disease, such as Crohn disease or sarcoidosis,[8] is present. Patients, especially children and adolescents, presenting with what appears to be granulomatous cheilitis or OFG should be very carefully evaluated for gastrointestinal symptoms, signs, and disease.[9]

A 2011 study of one of the largest cohorts (N=219) reports on the characteristics of patients with OFG.[10]



In granulomatous cheilitis, normal lip architecture is altered by lymphoedema and noncaseating granulomas in the lamina propria. TH 1 immunocytes produce interleukin 12 and RANTES/MIP-1alpha and granulomas. Expression of protease-activated receptor 1 and 2 occurs in orofacial granulomatosis (OFG). HLA typing may show HLA-A2 or HLA-A11.[11]

The cause of granulomatous cheilitis is unknown.[12] A genetic predisposition may exist in Melkersson-Rosenthal syndrome; siblings have been affected, and a plicated tongue may be present in otherwise unaffected relatives. Crohn disease, sarcoidosis, and OFG may present in a similar clinical fashion and with identical histologic findings. Similar findings have also been reported after liver transplantation in children.[13]

Dietary or other antigens are the most common identified cause of OFG.[14, 15] Contact antigens such as cobalt, gold, or mercury are sometimes implicated.[16] OFG may also result from reactions to some foods or medicaments, particularly cinnamon aldehyde and benzoates, but also butylated hydroxyanisole, dodecyl gallate, menthol, and monosodium glutamate.[17]

A summary of possibilities follows:

  • Genetics - Debate about link with HLA antigen
  • Food allergy - Various food additives thought to cause or precipitant event; 60% of individuals with condition are atopic (eczema, IgE levels); prime causative agents or exacerbation of disease
  • Allergy to dental material - No conclusive evidence
  • Infection - Studies have focused on Mycobacterium tuberculosis, Mycobacterium paratuberculosis, Saccharomyces cerevisiae, and Borrelia burgdorferi but provide insufficient evidence
  • Immunological - Hypothesis that no single antigen causes disease, rather a random influx of inflammatory cells; delayed sensitivity reaction rather than super antigen; results reflect an immunological nature
Contributor Information and Disclosures

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) Emeritus Professor, University College London; Visiting Professor, Universities of Athens, BPP, Edinburgh, Granada, Helsinki and Plymouth

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) is a member of the following medical societies: Academy of Medical Sciences, British Society for Oral Medicine, European Association for Oral Medicine, International Academy of Oral Oncology, International Association for Dental Research, International Association for Oral and Maxillofacial Pathology

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

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


David P Fivenson, MD Associate Director, St Joseph Mercy Hospital Dermatology Program, Ann Arbor, Michigan

David P Fivenson, MD is a member of the following medical societies: American Academy of Dermatology, Medical Dermatology Society, Michigan Dermatological Society, Michigan State Medical Society, Photomedicine Society, Society for Investigative Dermatology, and Wound Healing Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

  1. Grave B, McCullough M, Wiesenfeld D. Orofacial granulomatosis--a 20-year review. Oral Dis. 2009 Jan. 15 (1):46-51. [Medline].

  2. Khouri JM, Bohane TD, Day AS. Is orofacial granulomatosis in children a feature of Crohn's disease?. Acta Paediatr. 2005 Apr. 94(4):501-4. [Medline].

  3. Narbutt P, Dziki A. Re: Melkersson-Rosenthal syndrome as an early manifestation of Crohn's disease. Colorectal Dis. 2005 Jul. 7(4):420-1. [Medline].

  4. Scully C, Cochran KM, Russell RI, Ferguson MM, Ghouri MA, Lee FD, et al. Crohn's disease of the mouth: an indicator of intestinal involvement. Gut. 1982 Mar. 23(3):198-201. [Medline].

  5. Critchlow WA, Chang D. Cheilitis granulomatosa: a review. Head Neck Pathol. 2014 Jun. 8 (2):209-13. [Medline].

  6. Lazzerini M, Martelossi S, Cont G, Bersanini C, Ventura G, Fontana M, et al. Orofacial granulomatosis in children: think about Crohn's disease. Dig Liver Dis. 2015 Apr. 47 (4):338-41. [Medline].

  7. Troiano G, Dioguardi M, Giannatempo G, Laino L, Testa NF, Cocchi R, et al. Orofacial granulomatosis: clinical signs of different pathologies. Med Princ Pract. 2015. 24 (2):117-22. [Medline].

  8. Blinder D, Yahatom R, Taicher S. Oral manifestations of sarcoidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Apr. 83(4):458-61. [Medline].

  9. Girlich C, Bogenrieder T, Palitzsch KD, Schölmerich J, Lock G. Orofacial granulomatosis as initial manifestation of Crohn's disease: a report of two cases. Eur J Gastroenterol Hepatol. 2002 Aug. 14(8):873-6. [Medline].

  10. McCartan BE, Healy CM, McCreary CE, Flint SR, Rogers S, Toner ME. Characteristics of patients with orofacial granulomatosis. Oral Dis. 2011 Oct. 17(7):696-704. [Medline].

  11. Ketabchi S, Massi D, Ficarra G, et al. Expression of protease-activated receptor-1 and -2 in orofacial granulomatosis. Oral Dis. 2007 Jul. 13(4):419-25. [Medline].

  12. Tilakaratne WM, Freysdottir J, Fortune F. Orofacial granulomatosis: review on aetiology and pathogenesis. J Oral Pathol Med. 2008 Apr. 37(4):191-5. [Medline].

  13. Saalman R, Sundell S, Kullberg-Lindh C, Lövsund-Johannesson E, Jontell M. Long-standing oral mucosal lesions in solid organ-transplanted children-a novel clinical entity. Transplantation. 2010. 89:606.

  14. McKenna KE, Walsh MY, Burrows D. The Melkersson-Rosenthal syndrome and food additive hypersensitivity. Br J Dermatol. 1994 Dec. 131(6):921-2. [Medline].

  15. Morales C, Penarrocha M, Bagan JV, Burches E, Pelaez A. Immunological study of Melkersson-Rosenthal syndrome. Lack of response to food additive challenge. Clin Exp Allergy. 1995 Mar. 25(3):260-4. [Medline].

  16. Wong GA, Shear NH. Melkersson-Rosenthal syndrome associated with allergic contact dermatitis from octyl and dodecyl gallates. Contact Dermatitis. 2003 Nov. 49(5):266-7. [Medline].

  17. White A, Nunes C, Escudier M, et al. Improvement in orofacial granulomatosis on a cinnamon- and benzoate-free diet. Inflamm Bowel Dis. 2006 Jun. 12(6):508-14. [Medline].

  18. Khandpur S, Malhotra AK, Khanna N. Melkersson-Rosenthal syndrome with diffuse facial swelling and multiple cranial nerve palsies. J Dermatol. 2006 Jun. 33(6):411-4. [Medline].

  19. Saito T, Hida C, Tsunoda I, Tsukamoto T, Yamamoto T. Melkersson-Rosenthal syndrome: distal facial nerve branch palsies, masseter myopathy and corticosteroid treatment. Fukushima J Med Sci. 1994 Jun. 40(1):39-44. [Medline].

  20. Campbell H, Escudier M, Patel P, et al. Distinguishing orofacial granulomatosis from crohn's disease: two separate disease entities?. Inflamm Bowel Dis. 2011 Oct. 17(10):2109-15. [Medline].

  21. Fitzpatrick L, Healy CM, McCartan BE, Flint SR, McCreary CE, Rogers S. Patch testing for food-associated allergies in orofacial granulomatosis. J Oral Pathol Med. 2011 Jan. 40(1):10-3. [Medline].

  22. Banks T, Gada S. A comprehensive review of current treatments for granulomatous cheilitis. Br J Dermatol. 2012 May. 166 (5):934-7. [Medline].

  23. Campbell HE, Escudier MP, Patel P, Challacombe SJ, Sanderson JD, Lomer MC. Review article: cinnamon- and benzoate-free diet as a primary treatment for orofacial granulomatosis. Aliment Pharmacol Ther. 2011 Oct. 34 (7):687-701. [Medline].

  24. White A, Nunes C, Escudier M, Lomer MC, Barnard K, Shirlaw P, et al. Improvement in orofacial granulomatosis on a cinnamon- and benzoate-free diet. Inflamm Bowel Dis. 2006 Jun. 12 (6):508-14. [Medline].

  25. Campbell H, Escudier MP, Brostoff J, Patel P, Milligan P, Challacombe SJ, et al. Dietary intervention for oral allergy syndrome as a treatment in orofacial granulomatosis: a new approach?. J Oral Pathol Med. 2013 Aug. 42 (7):517-22. [Medline].

  26. Williams PM, Greenberg MS. Management of cheilitis granulomatosa. Oral Surg Oral Med Oral Pathol. 1991 Oct. 72(4):436-9. [Medline].

  27. Kruse-Losler B, Presser D, Metze D, Joos U. Surgical treatment of persistent macrocheilia in patients with Melkersson-Rosenthal syndrome and cheilitis granulomatosa. Arch Dermatol. 2005 Sep. 141(9):1085-91. [Medline].

  28. Tan Z, Zhang Y, Chen W, Gong W, Zhao J, Xu X. Recurrent facial palsy in Melkersson Rosenthal syndrome: total facial nerve decompression is effective to prevent further recurrence. Am J Otolaryngol. 2015 May-Jun. 36 (3):334-7. [Medline].

  29. Saalman R, Mattsson U, Jontell M. Orofacial granulomatosis in childhood-a clinical entity that may indicate Crohn's disease as well as food allergy. Acta Paediatr. 2009 Jul. 98(7):1162-7. [Medline].

  30. Kim SK, Lee ES. Orofacial granulomatosis associated with Crohn's disease. Ann Dermatol. 2010 May. 22(2):203-5. [Medline]. [Full Text].

  31. Kemmler N, Pfannschmidt N, Strohal R. Orofacial granulomatosis as first manifestation of Crohn's disease: successful treatment of both conditions with a combination of infliximab and dapsone. Acta Derm Venereol. 2012 Jul. 92(4):406-7. [Medline].

  32. Kano Y, Shiohara T, Yagita A, Nagashima M. Treatment of recalcitrant cheilitis granulomatosa with metronidazole. J Am Acad Dermatol. 1992 Oct. 27(4):629-30. [Medline].

  33. Fdez-Freire LR, Serrano Gotarredona A, Bernabeu Wittel J, Pulpillo Ruiz A, Cabrera R, Navarrete Ortega M, et al. Clofazimine as elective treatment for granulomatous cheilitis. J Drugs Dermatol. 2005 May-Jun. 4(3):374-7. [Medline].

  34. Tonkovic-Capin V, Galbraith SS, Rogers RS 3rd, Binion DG, Yancey KB. Cutaneous Crohn's disease mimicking Melkersson-Rosenthal syndrome: treatment with methotrexate. J Eur Acad Dermatol Venereol. 2006 Apr. 20(4):449-52. [Medline].

  35. Barry O, Barry J, Langan S, Murphy M, Fitzgibbon J, Lyons JF. Treatment of granulomatous cheilitis with infliximab. Arch Dermatol. 2005 Sep. 141(9):1080-2. [Medline].

  36. Sobjanek M, Wlodarkiewicz A, Zelazny I, Nowicki R, Michajlowski I, Sokolowska-Wojdylo M. Successful treatment of Melkersson-Rosenthal syndrome with dapsone and triamcinolone injections. J Eur Acad Dermatol Venereol. 2008 Aug. 22(8):1028-9; author reply 1027-8. [Medline].

  37. Hazey MA, Van Norman AJ, Armistead DL. Melkersson-Rosenthal Syndrome with migraine-like headaches treated with minocycline: a case report and review of the literature. W V Med J. 2009 Jan-Feb. 105(1):15-7. [Medline].

  38. Ishiguro E, Hatamochi A, Hamasaki Y, Ishikawa S, Yamazaki S. Successful treatment of granulomatous cheilitis with roxithromycin. J Dermatol. 2008 Sep. 35(9):598-600. [Medline].

Labial swelling and angular cheilitis.
Orofacial granulomatosis in a patient with Crohn disease showing showing lip and gingival swelling.
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