Gingival Manifestations of Orofacial Granulomatosis

Home , Geographic tongue, Gingival enlargement, Orofacial granulomatosis

OBSERVATION Gingival Manifestations of Orofacial Granulomatosis

Sı´lvia V. Lourenc¸o, DDS, PhD; Alice Z. C. Lobo, MD; Paula Boggio, MD; Fernando Fezzi, DDS; Alexandre Sebastia˜o, DDS; Marcello Menta S. Nico, MD

Background: Orofacial granulomatosis is a clinical en- gival biopsy. Histologic examination of all the gingival tity presenting with swelling of the facial and/or oral tis- biopsy specimens showed noncaseating granulomas, sues in association with histologic evidence of noncase- edema of the superficial lamina propria, and a chronic ating granulomatous inflammation. Labial swelling is the inflammatory infiltrate consisting predominantly of lym- most common finding. Compromise of the gingival and phocytes and multinucleated giant cells. Treatment op- periodontal tissues may occur but has rarely been de- tions included anti-inflammatory therapy associated with scribed in the literature. Our objective was to character- periodontal care. ize granulomatous gingivitis in patients with orofacial granulomatosis. Conclusion: Gingival tumefaction with histologic evidence of granulomatous inflammation may occur in oro- Observations: The study included 29 cases of orofa- facial granulomatosis and might be more common than cial granulomatosis seen in our clinic between January reported in the literature. 1, 1989, and December 31, 2006. Of these 29, 5 had clinical evidence of gingival tumefaction and underwent gin- Arch Dermatol. 2008;144(12):1627-1630

HE TERM OROFACIAL GRANU- ogy clinic and to present a detailed de- lomatosis describes a clini- scription of clinical and histopathological entity presenting with cal features of this particular presentation. swelling of the facial and/or oral tissues in association METHODS withT histologic evidence of noncaseating granulomatous inflammation. This clas- sification includes idiopathic disorders The study included 29 patients with orofacial such as Melkersson-Rosenthal syndrome granulomatosis (14 females and 15 males), examined between January 1, 1989, and Decem- and Miescher chronic granulomatous chei- ber 31, 2006, in the Oral Diseases Clinic of the litis, as well as the localized orofacial pre- Department of Dermatology, University of Saõ sentations of Crohn disease and sarcoid- Paulo. Patients included in the study had no osis.1-4 sign of disseminated granulomatous disease. All This condition has no sex or racial pre- patients underwent biopsy and, in those pre- dilection and the age at onset is highly vari- senting with clinical gingival changes, a gin- able, being more frequent in the second gival biopsy was also performed. Biopsy speci- and third decades of life. Orofacial swell- mens were fixed in 10% buffered formalin and ing may be intermittent initially but tends embedded in paraffin. Sections were stained to become chronic with fluctuations in se- with hematoxylin-eosin for histologic examination and with the histochemical techniques verity. It may also affect various sites or of periodic acid–Schiff, acid-fast bacilli, and be oligosymptomatic. Labial swelling is the Grocott for detection of infectious microor- most common finding, and it may in- ganisms. volve one or both lips, often in an asymmetrical manner.2,5,6 Specific gingival manifestations (granulomatous gingivitis) have RESULTS Author Affiliations: rarely been described in the literature but Department of General may occur in 21% to 26% of patients.1,5,7-9 Gingival-specific manifestations were Pathology, Dental School Detailed descriptions of these manifesta- detected in 5 of the 29 patients with oro- (Dr Lourenço), and Department tions are scarce, with few publications deal- facial granulomatosis examined. Their of Dermatology, Medical School 8 (Drs Lourenço, Lobo, Boggio, ing with this issue. clinical characteristics and outcome are Fezzi, Sebastiaõ, and Nico), The objective of this study was to de- summarized in the Table. The Figure University of Saõ Paulo, Saõ tect gingival manifestations in patients with illustrates the clinical and histologic Paulo, Brazil. orofacial granulomatosis in a dermatol- findings.

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Patient No.

Characteristic 1 (Figure, A and B) 2 (Figure, C and D) 3 (Figure, E and F) 4 (Figure, G and H) 5 (Figure, I and J) Patient age, y/sex 28/F 18/F 52/M 24/F 13/M Duration of symptoms, y 33423 Specific clinical Upper lip edema Upper lip edema Upper and lower lip Upper and lower lip Upper lip edema manifestation edema edema Gingival manifestation Gingival hyperplasia Marked hyperplasia of Marked hyperplasia of Marked hyperplasia of Marked hyperplasia of upper anterior upper and lower upper anterior upper anterior gingivae including gingivae, gingivae including gingivae including interdental papillae abscesses, and interdental papillae interdental papillae fistulas; severe periodontal disease and tooth mobility Tongue manifestation No No Yes (plicated and Yes (geographic No geographic tongue) tongue) Facial palsy No No No No No Treatment Dapsone (100 mg/d), Dapsone (100 mg/d), Dapsone (100 mg/d), Dapsone (100 mg/d), Dapsone (100 mg/d), intralesional intralesional oral prednisone (40 intralesional intralesional corticosteroid corticosteroid mg/d), intralesional corticosteroid corticosteroid infiltration (lip), infiltration (lip), corticosteroid infiltration (lip) infiltration (lip), and gingivoplasty and gingivoplasty infiltration (lip), and gingivoplasty and gingivoplasty Outcome Mild improvement Good improvement Good improvement Good improvement Good improvement (lost to follow-up (2-y follow-up) (3-y follow-up) (2-y follow-up) (1-y follow-up) after 1 y)

None of the patients had signs or symptoms of sys- orofacial swelling and histologically by noncaseating epi- temic disease. The histologic findings in the lip biopsy thelioid granulomas.1 The term orofacial granulomatosis specimens of the 29 patients examined included edema is nonspecific and is used to encompass clinical and his- and lymphocytic diffuse and perivascular inflammatory tologic features of more than 1 underlying etiology.1-3 infiltrate. In most specimens, loose and well-developed Melkersson-Rosenthal syndrome is the triad of recur- noncaseating granulomas were detected. The histopatho- rent or persistent orofacial swelling, peripheral facial nerve logical appearance of the 5 gingival biopsy specimens paralysis, and plicated tongue.5,7 However, few patients showed edema of the superficial lamina propria and an present with the complete syndrome. Hornstein2 re- infiltrate of chronic inflammatory cells consisting pre- ported that only 6 of 73 patients (8%) showed the com- dominantly of lymphocytes and multinucleate giant cells, plete triad. Cheilitis granulomatosa is the most frequent forming noncaseating granulomas (Figure, K and L). No finding and may occur as an isolated feature. Fissured birefringent foreign material was identified by polarized tongue (or plicated tongue) is not considered a pathog- light microscopy. Special histochemical stains detected nomonic sign of Melkersson-Rosenthal syndrome be- no fungi or acid-fast bacilli. cause it is common in the general population, and facial Complete blood cell count and results of kidney and nerve paralysis is usually of sudden onset and clinically liver function tests were normal in all patients. Chest ra- indistinguishable from Bell palsy.2,4 Several other symp- diographs were unremarkable. The diagnosis of orofa- toms, including intraoral, neurologic, ophthalmologic, cial granulomatosis with gingival involvement was es- and otologic manifestations, have been described in as- tablished on the basis of the clinical-histologic correlation sociation with orofacial granulomatosis/Melkersson- in the 5 cases presented. No patient was using any medi- Rosenthal syndrome.2,4,8 cations that could cause gingival hyperplasia; thus, the Among our initial cohort of 29 patients with orofa- possibility of drug-induced gingival hyperplasia was not cial granulomatosis, 5 (17%) presented with specific gin- considered. gival lesions. We found a wide range of gingival aspects Therapeutic modalities used included anti- in these cases. One patient (case 4) had mild gingival in- inflammatory drugs (intralesional and oral corticoste- volvement with edema of interdental papillae, and pa- roids and dapsone). Additional periodontal treatment was tients 2 and 5 had a diffuse infiltration. Two patients performed in all 5 cases of granulomatous gingivitis showed massive gingival enlargement (cases 1 and 3), (Table). Response to treatment was not uniform and associated with bleeding. In addition, patient 3 showed ranged from modest to almost complete improvement. periodontal fistulas and tooth mobility. All of these cases were confirmed to be due to specific infiltration of non- COMMENT caseating granulomas. Only a few studies describing gingival manifesta- Orofacial granulomatosis is a descriptive term used for a tions of orofacial granulomatosis/Melkersson- broad group of disorders affecting soft tissues of the face Rosenthal syndrome are available in the literature, espe- and oral cavity. It is characterized clinically by chronic cially regarding histologically confirmed granulomatous

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E F G H

I J K L

M N O P

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 ϫ40 and ϫ400, 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 ϫ100 [M] and ϫ400 [N, O, and P]).

gingivitis.1,5,7-9 According to these previous reports, the terations can be associated with erosion and pain.1,5 Gin- incidence of gingival alterations in Melkersson- gival manifestations of Melkersson-Rosenthal syndrome Rosenthal syndrome ranges from 21% to 26% and may occur particularly in the anterior parts of the mouth and antedate or occur simultaneously with lip manifesta- may extend from the gingival margin to the nonkera- tions. The main clinical characteristics of gingivae af- tinized alveolar mucosa. Histologically, gingival biopsy fected by Melkersson-Rosenthal syndrome differ from specimens are reported to show noncaseating epitheli- those of nonspecific inflammatory gingivitis. Gingival and oid granulomas.7 periodontal alterations include gum edema and ery- In orofacial granulomatosis/Melkersson-Rosenthal syn- thema, often with a patchy distribution.1,5,7-9 These al- drome, the classic histologic features are noncaseating

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 granulomas, multinucleated giant cells, and lymph- may be frustrating for the patient and physician. The gin- edema; however, these features may be absent, espe- giva may be involved in orofacial granulomatosis, and pa- cially in initial lesions. The findings are the same in lip tients usually present with erythema and edema of the and gingival specimens, and these granulomas are his- gingiva. The correct diagnosis and early treatment will tologically indistinguishable from those found in both be more comforting for the patient and yield better clini- gastrointestinal Crohn disease and systemic sarcoid- cal results, making increased diagnostic awareness im- osis.5,10 The histologic findings in our patients were simi- portant. lar in the lip and gingival specimens and showed a wide range of features. The most frequent change was edema Accepted for Publication: February 29, 2008. of the superficial lamina propria with prominent dilated Correspondence: Sı´lvia V. Lourenço, DDS, PhD, Facul- lymphatic vessels. In all 5 cases, chronic inflammatory dade de Odontologia da Universidade de Saõ Paulo, Av infiltrate with granulomatous arrangement was ob- Prof Lineu Prestes, 2227, Saõ Paulo, CEP: 05508-000, SP, served. Most granulomas were ill-defined, consisting of Brazil ([email protected]). epithelioid histiocytes and lymphocytes. Multinucleate Author Contributions: Drs Lourenço, Lobo, Boggio, and giant cells were present in all 5 gingival biopsy speci- Nico had full access to all of the data in the study and mens. Central necrosis was not observed in any of our take responsibility for the integrity of the data and ac- cases. curacy of the data analysis. Study concept and design: Orofacial granulomatosis may be a manifestation of Lourenço and Nico. Acquisition of data: Lourenço, Lobo, Crohn disease. In a study by Wiesenfeld et al,1 of a total Boggio, Fezzi, Sebastiaõ, and Nico. Analysis and inter- of 60 patients with orofacial granulomatosis, 6 (10%) had pretation of data: Lourenço, Lobo, Boggio, and Nico. Draft- gastrointestinal Crohn disease. Some authors recom- ing of the manuscript: Lourenço, Lobo, Boggio, and Nico. mend that patients presenting with orofacial granulo- Critical revision of the manuscript for important intellec- matosis be screened for the disease.11-13 None of the fore- tual content: Lourenço, Lobo, Boggio, and Nico. Admin- going evidence was found in the patients presented herein. istrative, technical, and material support: Lourenço, Fezzi, Orofacial granulomatosis may also be a manifesta- Sebastiaõ, and Nico. Study supervision: Lourenço and Nico. tion of sarcoidosis. In the same study by Wiesenfeld et Financial Disclosure: None reported. al,1 2 of these 60 patients with orofacial granulomatosis (3%) had the diagnosis of sarcoidosis. This disease should REFERENCES be considered as well in all patients with orofacial granulomatosis. The absence of clinical signs suggestive of sar- 1. Wiesenfeld D, Ferguson MM, Mitchell DN, et al. Oro-facial granulomatosis—a coidosis, a normal chest radiograph, and normal levels clinical and pathological analysis. QJMed. 1985;54(213):101-113. of serum angiotensin-converting enzyme make sarcoid- 2. Hornstein OP. Melkersson-Rosenthal syndrome: a challenge for dermatologists osis unlikely in the patients included in this study. to participate in the field of oral medicine. J Dermatol. 1997;24(5):281-296. 3. Armstrong DK, Burrows D. Orofacial granulomatosis. Int J Dermatol. 1995;34(12): Tuberculosis and leprosy should also be considered 830-833. as possibilities in patients with orofacial granulomato- 4. 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