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Gingival Manifestations of Orofacial Granulomatosis FREE

Sílvia V. Lourenço, DDS, PhD; Alice Z. C. Lobo, MD; Paula Boggio, MD; Fernando Fezzi, DDS; Alexandre Sebastião, DDS; Marcello Menta S. Nico, MD
[+] Author Affiliations

Author Affiliations: Department of General Pathology, Dental School (Dr Lourenço), and Department of Dermatology, Medical School (Drs Lourenço, Lobo, Boggio, Fezzi, Sebastião, and Nico), University of São Paulo, São Paulo, Brazil.


Arch Dermatol. 2008;144(12):1627-1630. doi:10.1001/archderm.144.12.1627.
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ABSTRACT

Background  Orofacial granulomatosis is a clinical entity presenting with swelling of the facial and/or oral tissues in association with histologic evidence of noncaseating granulomatous inflammation. Labial swelling is the most common finding. Compromise of the gingival and periodontal tissues may occur but has rarely been described in the literature. Our objective was to characterize granulomatous gingivitis in patients with orofacial granulomatosis.

Observations  The study included 29 cases of orofacial granulomatosis seen in our clinic between January 1, 1989, and December 31, 2006. Of these 29, 5 had clinical evidence of gingival tumefaction and underwent gingival biopsy. Histologic examination of all the gingival biopsy specimens showed noncaseating granulomas, edema of the superficial lamina propria, and a chronic inflammatory infiltrate consisting predominantly of lymphocytes and multinucleated giant cells. Treatment options included anti-inflammatory therapy associated with periodontal care.

Conclusion  Gingival tumefaction with histologic evidence of granulomatous inflammation may occur in orofacial granulomatosis and might be more common than reported in the literature.

Figures in this Article

The term orofacial granulomatosis describes a clinical entity presenting with swelling of the facial and/or oral tissues in association with histologic evidence of noncaseating granulomatous inflammation. This classification includes idiopathic disorders such as Melkersson-Rosenthal syndrome and Miescher chronic granulomatous cheilitis, as well as the localized orofacial presentations of Crohn disease and sarcoidosis.14

This condition has no sex or racial predilection and the age at onset is highly variable, being more frequent in the second and third decades of life. Orofacial swelling may be intermittent initially but tends to become chronic with fluctuations in severity. It may also affect various sites or be oligosymptomatic. Labial swelling is the most common finding, and it may involve one or both lips, often in an asymmetrical manner.2,5,6 Specific gingival manifestations (granulomatous gingivitis) have rarely been described in the literature but may occur in 21% to 26% of patients.1,5,79 Detailed descriptions of these manifestations are scarce, with few publications dealing with this issue.8

The objective of this study was to detect gingival manifestations in patients with orofacial granulomatosis in a dermatology clinic and to present a detailed description of clinical and histopathological features of this particular presentation.

METHODS

The study included 29 patients with orofacial granulomatosis (14 females and 15 males), examined between January 1, 1989, and December 31, 2006, in the Oral Diseases Clinic of the Department of Dermatology, University of São Paulo. Patients included in the study had no sign of disseminated granulomatous disease. All patients underwent biopsy and, in those presenting with clinical gingival changes, a gingival biopsy was also performed. Biopsy specimens were fixed in 10% buffered formalin and embedded in paraffin. Sections were stained with hematoxylin-eosin for histologic examination and with the histochemical techniques of periodic acid–Schiff, acid-fast bacilli, and Grocott for detection of infectious microorganisms.

RESULTS

Gingival-specific manifestations were detected in 5 of the 29 patients with orofacial granulomatosis examined. Their clinical characteristics and outcome are summarized in the Table. The Figure illustrates the clinical and histologic findings.

Place holder to copy figure label and caption
Figure.

Clinical and histopathological appearance in patients with orofacial granulomatosis. A, Cheilitis granulomatosa with edema and erythema of the upper lip in patient 1. B, Marked enlargement of the anterior upper gingivae in patient 1. C, Cheilitis granulomatosa with mild edema of the upper lip in patient 2. D, Mild diffuse gingival edema in patient 2. E, Exuberant cheilitis granulomatosa in patient 3. F, Massive infiltration and friability of the upper gum with periodontal fistula (arrow) in patient 3. G, Asymmetrical edema of the upper and lower lip in patient 4. H, Mild edema of the interdental papillae in patient 4. I, Facial edema and enlargement of the upper lip in patient 5. J, Diffuse enlargement of upper and lower gingivae in patient 5. K and L, Histopathological aspects of gingival granulomatosis in patient 3, showing edema and lymphocytic infiltration of the lamina propria. There is granuloma formation with presence of multinucleate giant cells (hematoxylin-eosin, original magnification ×40 and ×400, respectively). M-P, Histopathological aspects of gingival granulomatosis in patients 1, 2, 4, and 5, respectively. In M, note the compact granulomatous aggregate in the lamina propria. In N through P there is granuloma formation with presence of multinucleate giant cells (arrows) and edema (hematoxylin-eosin, original magnification ×100 [M] and ×400 [N, O, and P]).

Graphic Jump Location
Table Graphic Jump LocationTable. Patients With Orofacial Granulomatosis Manifesting Granulomatous Gingivitis

None of the patients had signs or symptoms of systemic disease. The histologic findings in the lip biopsy specimens of the 29 patients examined included edema and lymphocytic diffuse and perivascular inflammatory infiltrate. In most specimens, loose and well-developed noncaseating granulomas were detected. The histopathological appearance of the 5 gingival biopsy specimens showed edema of the superficial lamina propria and an infiltrate of chronic inflammatory cells consisting predominantly of lymphocytes and multinucleate giant cells, forming noncaseating granulomas (Figure, K and L). No birefringent foreign material was identified by polarized light microscopy. Special histochemical stains detected no fungi or acid-fast bacilli.

Complete blood cell count and results of kidney and liver function tests were normal in all patients. Chest radiographs were unremarkable. The diagnosis of orofacial granulomatosis with gingival involvement was established on the basis of the clinical-histologic correlation in the 5 cases presented. No patient was using any medications that could cause gingival hyperplasia; thus, the possibility of drug-induced gingival hyperplasia was not considered.

Therapeutic modalities used included anti-inflammatory drugs (intralesional and oral corticosteroids and dapsone). Additional periodontal treatment was performed in all 5 cases of granulomatous gingivitis (Table). Response to treatment was not uniform and ranged from modest to almost complete improvement.

COMMENT

Orofacial granulomatosis is a descriptive term used for a broad group of disorders affecting soft tissues of the face and oral cavity. It is characterized clinically by chronic orofacial swelling and histologically by noncaseating epithelioid granulomas.1 The term orofacial granulomatosis is nonspecific and is used to encompass clinical and histologic features of more than 1 underlying etiology.13

Melkersson-Rosenthal syndrome is the triad of recurrent or persistent orofacial swelling, peripheral facial nerve paralysis, and plicated tongue.5,7 However, few patients present with the complete syndrome. Hornstein2 reported that only 6 of 73 patients (8%) showed the complete triad. Cheilitis granulomatosa is the most frequent finding and may occur as an isolated feature. Fissured tongue (or plicated tongue) is not considered a pathognomonic sign of Melkersson-Rosenthal syndrome because it is common in the general population, and facial nerve paralysis is usually of sudden onset and clinically indistinguishable from Bell palsy.2,4 Several other symptoms, including intraoral, neurologic, ophthalmologic, and otologic manifestations, have been described in association with orofacial granulomatosis/Melkersson-Rosenthal syndrome.2,4,8

Among our initial cohort of 29 patients with orofacial granulomatosis, 5 (17%) presented with specific gingival lesions. We found a wide range of gingival aspects in these cases. One patient (case 4) had mild gingival involvement with edema of interdental papillae, and patients 2 and 5 had a diffuse infiltration. Two patients showed massive gingival enlargement (cases 1 and 3), associated with bleeding. In addition, patient 3 showed periodontal fistulas and tooth mobility. All of these cases were confirmed to be due to specific infiltration of noncaseating granulomas.

Only a few studies describing gingival manifestations of orofacial granulomatosis/Melkersson-Rosenthal syndrome are available in the literature, especially regarding histologically confirmed granulomatous gingivitis.1,5,79 According to these previous reports, the incidence of gingival alterations in Melkersson-Rosenthal syndrome ranges from 21% to 26% and may antedate or occur simultaneously with lip manifestations. The main clinical characteristics of gingivae affected by Melkersson-Rosenthal syndrome differ from those of nonspecific inflammatory gingivitis. Gingival and periodontal alterations include gum edema and erythema, often with a patchy distribution.1,5,79 These alterations can be associated with erosion and pain.1,5 Gingival manifestations of Melkersson-Rosenthal syndrome occur particularly in the anterior parts of the mouth and may extend from the gingival margin to the nonkeratinized alveolar mucosa. Histologically, gingival biopsy specimens are reported to show noncaseating epithelioid granulomas.7

In orofacial granulomatosis/Melkersson-Rosenthal syndrome, the classic histologic features are noncaseating granulomas, multinucleated giant cells, and lymphedema; however, these features may be absent, especially in initial lesions. The findings are the same in lip and gingival specimens, and these granulomas are histologically indistinguishable from those found in both gastrointestinal Crohn disease and systemic sarcoidosis.5,10 The histologic findings in our patients were similar in the lip and gingival specimens and showed a wide range of features. The most frequent change was edema of the superficial lamina propria with prominent dilated lymphatic vessels. In all 5 cases, chronic inflammatory infiltrate with granulomatous arrangement was observed. Most granulomas were ill-defined, consisting of epithelioid histiocytes and lymphocytes. Multinucleate giant cells were present in all 5 gingival biopsy specimens. Central necrosis was not observed in any of our cases.

Orofacial granulomatosis may be a manifestation of Crohn disease. In a study by Wiesenfeld et al,1 of a total of 60 patients with orofacial granulomatosis, 6 (10%) had gastrointestinal Crohn disease. Some authors recommend that patients presenting with orofacial granulomatosis be screened for the disease.1113 None of the foregoing evidence was found in the patients presented herein.

Orofacial granulomatosis may also be a manifestation of sarcoidosis. In the same study by Wiesenfeld et al,1 2 of these 60 patients with orofacial granulomatosis (3%) had the diagnosis of sarcoidosis. This disease should be considered as well in all patients with orofacial granulomatosis. The absence of clinical signs suggestive of sarcoidosis, a normal chest radiograph, and normal levels of serum angiotensin-converting enzyme make sarcoidosis unlikely in the patients included in this study.

Tuberculosis and leprosy should also be considered as possibilities in patients with orofacial granulomatosis1; however, our patients had no clinical or histopathological evidence of these disorders either.

It is not clear how much investigation is appropriate for each patient with orofacial granulomatosis. It is important that suspected cases of orofacial granulomatosis be investigated appropriately to exclude other similar disorders. However, unwarranted and unpleasant investigations should be avoided when possible.11

In orofacial granulomatosis/Melkersson-Rosenthal syndrome the prognosis is difficult to predict. Occasionally the disease may have spontaneous regression, although the process may take years. In a long-term follow-up of 5 cases, Field and Tyldesley14 reported gradual resolution of buccal lesions and edema of the lips in all patients during a 10-year period. Treatment usually is necessary, and no single approach has been universally successful. Management of dental and periodontal conditions are important for patient outcome,10 as in patient 3 described herein.

In conclusion, orofacial granulomatosis may cause significant cosmetic and functional problems, has an uncertain cause, may be associated with systemic disease, and has an unpredictable response to treatment, which may be frustrating for the patient and physician. The gingiva may be involved in orofacial granulomatosis, and patients usually present with erythema and edema of the gingiva. The correct diagnosis and early treatment will be more comforting for the patient and yield better clinical results, making increased diagnostic awareness important.

ARTICLE INFORMATION

Correspondence: Sílvia V. Lourenço, DDS, PhD, Faculdade de Odontologia da Universidade de São Paulo, Av Prof Lineu Prestes, 2227, São Paulo, CEP: 05508-000, SP, Brazil (silvialourenco.70@terra.com.br).

Accepted for Publication: February 29, 2008.

Author Contributions: Drs Lourenço, Lobo, Boggio, and Nico had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: Lourenço and Nico. Acquisition of data: Lourenço, Lobo, Boggio, Fezzi, Sebastião, and Nico. Analysis and interpretation of data: Lourenço, Lobo, Boggio, and Nico. Drafting of the manuscript: Lourenço, Lobo, Boggio, and Nico. Critical revision of the manuscript for important intellectual content: Lourenço, Lobo, Boggio, and Nico. Administrative, technical, and material support: Lourenço, Fezzi, Sebastião, and Nico. Study supervision: Lourenço and Nico.

Financial Disclosure: None reported.

REFERENCES

Wiesenfeld  DFerguson  MMMitchell  DN  et al.  Oro-facial granulomatosis—a clinical and pathological analysis. Q J Med 1985;54 (213) 101- 113
PubMed
Hornstein  OP Melkersson-Rosenthal syndrome: a challenge for dermatologists to participate in the field of oral medicine. J Dermatol 1997;24 (5) 281- 296
PubMed
Armstrong  DKBurrows  D Orofacial granulomatosis. Int J Dermatol 1995;34 (12) 830- 833
PubMed Link to Article
Sciubba  JJSaid-Al-Naief  N Orofacial granulomatosis: presentation, pathology and management of 13 cases. J Oral Pathol Med 2003;32 (10) 576- 585
PubMed Link to Article
Zimmer  WMRogers  RS  IIIReeve  CMSheridan  PJMinn  R Orofacial manifestations of Melkersson-Rosenthal syndrome: a study of 42 patients and review of 220 cases from the literature. Oral Surg Oral Med Oral Pathol 1992;74 (5) 610- 619
PubMed Link to Article
van der Waal  RIFSchulten  EAJMvan de Scheur  MRWauters  IMPMJStarink  TMvan der Waal  I Cheilitis granulomatosa. J Eur Acad Dermatol Venereol 2001;15 (6) 519- 523
PubMed Link to Article
Worsaae  NChristensen  KCSchiodt  MReibel  J Melkersson-Rosenthal syndrome and cheilitis granulomatosa: a clinicopathological study of thirty-three patients with special reference to their oral lesions. Oral Surg Oral Med Oral Pathol 1982;54 (4) 404- 413
PubMed Link to Article
Worsaae  NPindborg  JJ Granulomatous gingival manifestations of Melkersson-Rosenthal syndrome. Oral Surg Oral Med Oral Pathol 1980;49 (2) 131- 138
PubMed Link to Article
Levenson  MJIngerman  MGrimes  CAnand  KV Melkersson-Rosenthal syndrome. Arch Otolaryngol 1984;110 (8) 540- 542
PubMed Link to Article
Bogenrieder  TRogler  GVogt  TLandthaler  MStolz  W Orofacial granulomatosis as the initial presentation of Crohn's disease in an adolescent. Dermatology 2003;206 (3) 273- 278
PubMed Link to Article
Clayden  AMBleys  CMJones  SFSavage  NWAldred  MJ Orofacial granulomatosis: a diagnostic problem for the unwary and management dilemma: case reports. Aust Dent J 1997;42 (4) 228- 232
PubMed Link to Article
Pryce  DWKing  CM Orofacial granulomatosis associated with delayed hypersensitivity to cobalt. Clin Exp Dermatol 1990;15 (5) 384- 386
PubMed Link to Article
Plauth  MJenss  HMeyle  J Oral manifestations of Crohn's disease: an analysis of 79 cases. J Clin Gastroenterol 1991;13 (1) 29- 37
PubMed Link to Article
Field  EATyldesley  WR Oral Crohn's disease revisited—a 10 year review. Br J Oral Maxillofac Surg 1989;27 (2) 114- 123
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Clinical and histopathological appearance in patients with orofacial granulomatosis. A, Cheilitis granulomatosa with edema and erythema of the upper lip in patient 1. B, Marked enlargement of the anterior upper gingivae in patient 1. C, Cheilitis granulomatosa with mild edema of the upper lip in patient 2. D, Mild diffuse gingival edema in patient 2. E, Exuberant cheilitis granulomatosa in patient 3. F, Massive infiltration and friability of the upper gum with periodontal fistula (arrow) in patient 3. G, Asymmetrical edema of the upper and lower lip in patient 4. H, Mild edema of the interdental papillae in patient 4. I, Facial edema and enlargement of the upper lip in patient 5. J, Diffuse enlargement of upper and lower gingivae in patient 5. K and L, Histopathological aspects of gingival granulomatosis in patient 3, showing edema and lymphocytic infiltration of the lamina propria. There is granuloma formation with presence of multinucleate giant cells (hematoxylin-eosin, original magnification ×40 and ×400, respectively). M-P, Histopathological aspects of gingival granulomatosis in patients 1, 2, 4, and 5, respectively. In M, note the compact granulomatous aggregate in the lamina propria. In N through P there is granuloma formation with presence of multinucleate giant cells (arrows) and edema (hematoxylin-eosin, original magnification ×100 [M] and ×400 [N, O, and P]).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Patients With Orofacial Granulomatosis Manifesting Granulomatous Gingivitis

References

Wiesenfeld  DFerguson  MMMitchell  DN  et al.  Oro-facial granulomatosis—a clinical and pathological analysis. Q J Med 1985;54 (213) 101- 113
PubMed
Hornstein  OP Melkersson-Rosenthal syndrome: a challenge for dermatologists to participate in the field of oral medicine. J Dermatol 1997;24 (5) 281- 296
PubMed
Armstrong  DKBurrows  D Orofacial granulomatosis. Int J Dermatol 1995;34 (12) 830- 833
PubMed Link to Article
Sciubba  JJSaid-Al-Naief  N Orofacial granulomatosis: presentation, pathology and management of 13 cases. J Oral Pathol Med 2003;32 (10) 576- 585
PubMed Link to Article
Zimmer  WMRogers  RS  IIIReeve  CMSheridan  PJMinn  R Orofacial manifestations of Melkersson-Rosenthal syndrome: a study of 42 patients and review of 220 cases from the literature. Oral Surg Oral Med Oral Pathol 1992;74 (5) 610- 619
PubMed Link to Article
van der Waal  RIFSchulten  EAJMvan de Scheur  MRWauters  IMPMJStarink  TMvan der Waal  I Cheilitis granulomatosa. J Eur Acad Dermatol Venereol 2001;15 (6) 519- 523
PubMed Link to Article
Worsaae  NChristensen  KCSchiodt  MReibel  J Melkersson-Rosenthal syndrome and cheilitis granulomatosa: a clinicopathological study of thirty-three patients with special reference to their oral lesions. Oral Surg Oral Med Oral Pathol 1982;54 (4) 404- 413
PubMed Link to Article
Worsaae  NPindborg  JJ Granulomatous gingival manifestations of Melkersson-Rosenthal syndrome. Oral Surg Oral Med Oral Pathol 1980;49 (2) 131- 138
PubMed Link to Article
Levenson  MJIngerman  MGrimes  CAnand  KV Melkersson-Rosenthal syndrome. Arch Otolaryngol 1984;110 (8) 540- 542
PubMed Link to Article
Bogenrieder  TRogler  GVogt  TLandthaler  MStolz  W Orofacial granulomatosis as the initial presentation of Crohn's disease in an adolescent. Dermatology 2003;206 (3) 273- 278
PubMed Link to Article
Clayden  AMBleys  CMJones  SFSavage  NWAldred  MJ Orofacial granulomatosis: a diagnostic problem for the unwary and management dilemma: case reports. Aust Dent J 1997;42 (4) 228- 232
PubMed Link to Article
Pryce  DWKing  CM Orofacial granulomatosis associated with delayed hypersensitivity to cobalt. Clin Exp Dermatol 1990;15 (5) 384- 386
PubMed Link to Article
Plauth  MJenss  HMeyle  J Oral manifestations of Crohn's disease: an analysis of 79 cases. J Clin Gastroenterol 1991;13 (1) 29- 37
PubMed Link to Article
Field  EATyldesley  WR Oral Crohn's disease revisited—a 10 year review. Br J Oral Maxillofac Surg 1989;27 (2) 114- 123
PubMed Link to Article

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