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Cheilitis glandularis: An unusual presentation in a patient with HIV infection
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Vol. 95 No. 2 February 2003
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY CLINICAL NOTES
Cheilitis glandularis: An unusual presentation in a patient with HIV infection Jair C. Lea˜o, BDS, MSc, PhD,a Ana Micaeli C. Ferreira, BDS,b Sarita Martins, MD, PhD,c Ma´rcio Lobo Jardim, MD, PhD,d A. William Barrett, PhD, FDSRCS, MRC Path,e Crispian Scully, CBE, MD, PhD, MDS, FDSRCPS, FDSRCS, FFDRCSI, FDSRCSE, FRCPath, FMedSci,f and Stephen R. Porter, MD, PhD, FDSRCS, FDSRCSE,g Recife, Brazil, and London, United Kingdom UNIVERSIDADE FEDERAL DE PERNAMBUCO AND UNIVERSITY COLLEGE LONDON
Cheilitis glandularis is a rare disorder of unknown etiology characterized by inflammation of the minor salivary glands of the lower lip. The present report details the features of a patient who presented with cheilitis glandularis and was subsequently found to also have undiagnosed HIV infection. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:142-4)
Cheilitis glandularis (CG) is a rare disorder that manifests clinically as labial swelling and ulceration. It was first described by Volkman1 in 1870 as an inflammatory disease of labial salivary glands. The disease is localized almost exclusively to the lower lip, especially the contact zone between the lips,2 although there have been occasional reports of CG affecting the upper lips and palate.3,4 Affected individuals usually have swell-
ing, eversion, and protrusion of the lower lip as a result of inflammation of the minor labial salivary glands. The orifices of the minor salivary gland ducts are dilated and inflamed, and a mucopurulent secretion may be expelled from the ducts when the lip is compressed.5 The present report details the features of a patient who presented with CG and was subsequently found to also have HIV infection.
a
CASE REPORT
Associate Professor of Stomatology, Departamento de Clı´nica e Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil. b Lecturer of Stomatology, Departamento de Clı´nica e Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil. c Associate Professor of Dermatology, Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Brazil. d Professor of Dermatology, Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Brazil. e Senior Lecturer, Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. f Dean and Professor of Special Needs in Dentistry, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. g Professor and Head of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. Received for publication Mar 5, 2002; returned for revision May 20, 2002; accepted for publication Jul 10, 2002. © 2003, Mosby, Inc. 1079-2104/2003/$30.00 ⫹ 0 doi:10.1067/moe.2003.27
142
A 40-year-old man attended the outpatient clinic of the Hospital das Clı´nicas, Universidade Federal de Pernambuco, Recife, Brazil, complaining of painful ulceration of the lower lip of approximately 6 months’ duration (Fig 1). There was no identifiable cause for the ulceration, and the patient had never had any relevant treatment. A review of symptoms showed that the patient had lost 4 kg in weight during the previous month and had recently developed ill-defined tremors. The patient’s medical history included a history of rectal bleeding as a result of hemorrhoids, recent grand mal–like seizures, and previous episodes of infective syphilis and genital gonorrhea. The patient smoked at least 20 cigarettes per day and drank around 21 units of alcohol per week. He denied recreational drug use or having sex with other men. Extraoral examination showed no cervical lymphadenopathy. There was extensive, deep, irregular ulceration of the skin and mucosa of the lower lip (Fig 1) but no other oral or dermatologic evidence of possible granulomatous or allergic disease. The working diagnosis included primary chancre,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 95, Number 2
Fig 1. Initial presentation showing ulceration of the skin and mucosa of the lower lip.
HIV-related ulceration, vesiculobullous disease (particularly erythema multiforme), cheilitis granulomatosa, and CG. Subsequent investigations showed the patient to have no serologic evidence of recent Treponema pallidum infection, when assessed with relevant specific (fluorescent treponemal antibodies) and nonspecific (Venereal Disease Research Laboratory) assays. After appropriate counseling, the patient was found to be HIV seropositive as tested by enzyme-linked immunosorbent assay and immunofluorescence. He had a peripheral blood CD4⫹ T-cell count of 106 cells per mm3 (normal: more than 500 per mm3), a CD4⫹/CD8⫹ ratio of 0.2 (normal range: 0.93 to 1.12), and an HIV viral load of 15,000 log 4.18. Histopathologic examination of lesional tissue showed ulceration and loss of tissue architecture. There were areas of degenerated keratinizing stratified squamous epithelium with inflammation of the labial salivary glands, abundant mucopurulent material, and foreign vegetable matter. Acute and chronic inflammatory cells had infiltrated the surrounding tissues (Figs 2 and 3). There were no granulomas, and staining with hematoxylin-eosin and periodic acid/Schiff reagent showed no microorganisms. Hence, on the basis of the clinical, histologic, and serologic findings, the patient was diagnosed as having CG and HIV infection. The patient commenced highly active antiretroviral therapy (HAART: stavudine [d4T], 40 mg to be taken twice a day; didanosine [dideoxyinosine], 200 mg to be taken twice a day; and indinavir, 800 mg to be taken 3 times a day) together with sulfadiazine, 3 g every day; fluconazole, 150 mg every day; and folic acid and vitamin B12 supplements. During the following 3 months, the labial ulceration gradually improved. The CD4⫹ T-cell count increased to 132 cells per mm,3 and the HIV viral load fell to 860 log 2.93. The labial ulceration fully resolved after 5 months of therapy with the aforementioned drugs (Fig 4).
DISCUSSION CG occurs equally in male and female adults5,6 and can occasionally arise in children.7 CG association with
Lea˜o et al 143
Fig 2. Histopathologic slide showing inspissated mucus (arrow) containing chronic and acute inflammatory cells, which had also infiltrated the surrounding tissues (original magnification ⫻10; hematoxylin-eosin stain).
Fig 3. View of Fig 2 (original magnification ⫻40).
HIV infection has not been previously described. This association, however, is probably coincidental, because cell-mediated immunosuppression is unlikely to be of significance in the etiology of CG. The precise etiology of CG remains unknown, although associations with syphilis1 and other more illdefined bacterial infections,7 poor hygiene,3,5,8 tobacco use,8 actinic exposure,5,8,9 and emotional disturbance10 have been suggested. A genetic predisposition3,5,7 has also been proposed. The term suppurative stomatitis glandularis has also been suggested to describe CG.11,12 Indeed, the terminology used in the previous relevant literature is confusing. Granulomatous cheilitis is unrelated to CG, the former being a localized presentation of sarcoidosis or an atypical granulomatous disease.13,14 CG may be classified into 3 types on the basis of the severity of the disease: simplex, superficial suppurative,
144 Lea˜ o et al
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY February 2003
Gram-negative microorganisms, played a role in the clearance of signs and symptoms. In conclusion, the present report details the clinical and histopathologic features of CG in a patient coincidentally found to have HIV infection. REFERENCES
Fig 4. Complete remission of the lesion.
and deep suppurative. The last 2 types represent a stage in which there is bacterial infection, clinically characterized by increased inflammation, suppuration, and ulceration of the lip.3 The deep suppurative type of CG has also been termed cheilitis apostematosa or myxadenitis labialis, whereas the superficial suppurative has also been termed Baelz’s disease.5 The histopathologic findings of CG are nonspecific but include local chronic sialadenitis and ductal dilatation. Dysplastic epithelial changes may occasionally occur,15 but, although associated carcinoma of the lower lip has been reported, CG is still considered to be a benign disorder that should be managed by conservative means.3,15 There are no detailed randomized studies of the treatment of CG. Surgery—for example, vermilionectomy— has been suggested to be effective. However, albeit rarely, mucoceles can occur after surgery.3,16 This patient, however, did not require vermilionectomy because the lesion fully resolved after 5 months of HAART and systemic antibacterials, despite the CD4⫹ T-cell counts only increasing marginally. The reason for the remission is unclear, but CG has been associated with bacterial infection.7 It is thus possible that sulfadiazine, being effective against Gram-positive and
1. Volkman RV. Einige falle von cheilitis glandularis apostematosa. Arch Pathol Anat 1870;50:142-4. 2. Fonseca A, Souza EM. Dermatologia Clı´nica. Rio de Janeiro: Guanabara Koogan; 1984. p. 584. 3. Rogers RS 3rd, Bekic M. Diseases of the lips. Semin Cutan Med Surg 1997;16:328-36. 4. Winchester L, Scully C, Prime SS, Eveson JW. Cheilitis glandularis: a case affecting the upper lip. Oral Surg Oral Med Oral Pathol 1986;62:654-6. 5. Weir TW, Johnson WC. Cheilitis glandularis. J Oral Med 1971; 103:433-7. 6. Yacobi R, Brown DA. Cheilitis glandularis. J Am Dent Assoc 1989;118:317-8. 7. Doku HC. Cheilitis glandularis. Oral Surg Oral Med Oral Pathol 1965;20:563-1. 8. Everett FG, Holder D. Cheilitis glandularis apostematosa. Oral Surg Oral Med Oral Pathol 1955;8:405-13. 9. Rada DC. Cheilitis glandularis: a disorder of ductal ectasia. J Dermatol Surg Oncol 1985;11:372-5. 10. Woodburne AR, Philpott OS. Cheilitis glandularis: a manifestation of emotional disturbance. Arch Dermatol Syph 1950;62: 820-8. 11. Lederman DA. Suppurative stomatitis glandularis. Oral Surg Oral Med Oral Pathol 1994;78:319-22. 12. Williams HK, Williams DM. Persistent sialadenitis of the minor glands: stomatitis glandularis. Br J Oral Maxillofac Surg 1989; 27:212-6. 13. Stuller CB. Cheilitis glandularis. Oral Surg Oral Med Oral Pathol 1982;53:602-5. 14. Scully CM, Bagan J, Eiser D, Porter SR, Rogers RS. Dermatology of the lips. Oxford: Isis Medical Media; 2000. p. 81-9. 15. Michalowski R. Cheilitis glandularis, heterotropic salivary glands and squamous cell carcinoma of the lip. Br J Dermatol 1962;74:445-59. 16. Shah JS, Shah SG, Kubavat HJ, Dayal PK. Cheilitis glandularis. J Pierre Fauchard Acad 1992;6:103-6. Reprint requests: Jair Carneiro Lea˜ o, BDS, MSc, PhD Departamento de Clı´nica e Odontologia Preventiva Universidade Federal de Pernambuco Av. Prof. Moraes Rego, 1235 Recife, PE Brazil CEP 50670-901 [email protected]
Vol. 95 No. 2 February 2003
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY CLINICAL NOTES
Cheilitis glandularis: An unusual presentation in a patient with HIV infection Jair C. Lea˜o, BDS, MSc, PhD,a Ana Micaeli C. Ferreira, BDS,b Sarita Martins, MD, PhD,c Ma´rcio Lobo Jardim, MD, PhD,d A. William Barrett, PhD, FDSRCS, MRC Path,e Crispian Scully, CBE, MD, PhD, MDS, FDSRCPS, FDSRCS, FFDRCSI, FDSRCSE, FRCPath, FMedSci,f and Stephen R. Porter, MD, PhD, FDSRCS, FDSRCSE,g Recife, Brazil, and London, United Kingdom UNIVERSIDADE FEDERAL DE PERNAMBUCO AND UNIVERSITY COLLEGE LONDON
Cheilitis glandularis is a rare disorder of unknown etiology characterized by inflammation of the minor salivary glands of the lower lip. The present report details the features of a patient who presented with cheilitis glandularis and was subsequently found to also have undiagnosed HIV infection. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:142-4)
Cheilitis glandularis (CG) is a rare disorder that manifests clinically as labial swelling and ulceration. It was first described by Volkman1 in 1870 as an inflammatory disease of labial salivary glands. The disease is localized almost exclusively to the lower lip, especially the contact zone between the lips,2 although there have been occasional reports of CG affecting the upper lips and palate.3,4 Affected individuals usually have swell-
ing, eversion, and protrusion of the lower lip as a result of inflammation of the minor labial salivary glands. The orifices of the minor salivary gland ducts are dilated and inflamed, and a mucopurulent secretion may be expelled from the ducts when the lip is compressed.5 The present report details the features of a patient who presented with CG and was subsequently found to also have HIV infection.
a
CASE REPORT
Associate Professor of Stomatology, Departamento de Clı´nica e Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil. b Lecturer of Stomatology, Departamento de Clı´nica e Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil. c Associate Professor of Dermatology, Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Brazil. d Professor of Dermatology, Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Brazil. e Senior Lecturer, Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. f Dean and Professor of Special Needs in Dentistry, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. g Professor and Head of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, United Kingdom. Received for publication Mar 5, 2002; returned for revision May 20, 2002; accepted for publication Jul 10, 2002. © 2003, Mosby, Inc. 1079-2104/2003/$30.00 ⫹ 0 doi:10.1067/moe.2003.27
142
A 40-year-old man attended the outpatient clinic of the Hospital das Clı´nicas, Universidade Federal de Pernambuco, Recife, Brazil, complaining of painful ulceration of the lower lip of approximately 6 months’ duration (Fig 1). There was no identifiable cause for the ulceration, and the patient had never had any relevant treatment. A review of symptoms showed that the patient had lost 4 kg in weight during the previous month and had recently developed ill-defined tremors. The patient’s medical history included a history of rectal bleeding as a result of hemorrhoids, recent grand mal–like seizures, and previous episodes of infective syphilis and genital gonorrhea. The patient smoked at least 20 cigarettes per day and drank around 21 units of alcohol per week. He denied recreational drug use or having sex with other men. Extraoral examination showed no cervical lymphadenopathy. There was extensive, deep, irregular ulceration of the skin and mucosa of the lower lip (Fig 1) but no other oral or dermatologic evidence of possible granulomatous or allergic disease. The working diagnosis included primary chancre,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 95, Number 2
Fig 1. Initial presentation showing ulceration of the skin and mucosa of the lower lip.
HIV-related ulceration, vesiculobullous disease (particularly erythema multiforme), cheilitis granulomatosa, and CG. Subsequent investigations showed the patient to have no serologic evidence of recent Treponema pallidum infection, when assessed with relevant specific (fluorescent treponemal antibodies) and nonspecific (Venereal Disease Research Laboratory) assays. After appropriate counseling, the patient was found to be HIV seropositive as tested by enzyme-linked immunosorbent assay and immunofluorescence. He had a peripheral blood CD4⫹ T-cell count of 106 cells per mm3 (normal: more than 500 per mm3), a CD4⫹/CD8⫹ ratio of 0.2 (normal range: 0.93 to 1.12), and an HIV viral load of 15,000 log 4.18. Histopathologic examination of lesional tissue showed ulceration and loss of tissue architecture. There were areas of degenerated keratinizing stratified squamous epithelium with inflammation of the labial salivary glands, abundant mucopurulent material, and foreign vegetable matter. Acute and chronic inflammatory cells had infiltrated the surrounding tissues (Figs 2 and 3). There were no granulomas, and staining with hematoxylin-eosin and periodic acid/Schiff reagent showed no microorganisms. Hence, on the basis of the clinical, histologic, and serologic findings, the patient was diagnosed as having CG and HIV infection. The patient commenced highly active antiretroviral therapy (HAART: stavudine [d4T], 40 mg to be taken twice a day; didanosine [dideoxyinosine], 200 mg to be taken twice a day; and indinavir, 800 mg to be taken 3 times a day) together with sulfadiazine, 3 g every day; fluconazole, 150 mg every day; and folic acid and vitamin B12 supplements. During the following 3 months, the labial ulceration gradually improved. The CD4⫹ T-cell count increased to 132 cells per mm,3 and the HIV viral load fell to 860 log 2.93. The labial ulceration fully resolved after 5 months of therapy with the aforementioned drugs (Fig 4).
DISCUSSION CG occurs equally in male and female adults5,6 and can occasionally arise in children.7 CG association with
Lea˜o et al 143
Fig 2. Histopathologic slide showing inspissated mucus (arrow) containing chronic and acute inflammatory cells, which had also infiltrated the surrounding tissues (original magnification ⫻10; hematoxylin-eosin stain).
Fig 3. View of Fig 2 (original magnification ⫻40).
HIV infection has not been previously described. This association, however, is probably coincidental, because cell-mediated immunosuppression is unlikely to be of significance in the etiology of CG. The precise etiology of CG remains unknown, although associations with syphilis1 and other more illdefined bacterial infections,7 poor hygiene,3,5,8 tobacco use,8 actinic exposure,5,8,9 and emotional disturbance10 have been suggested. A genetic predisposition3,5,7 has also been proposed. The term suppurative stomatitis glandularis has also been suggested to describe CG.11,12 Indeed, the terminology used in the previous relevant literature is confusing. Granulomatous cheilitis is unrelated to CG, the former being a localized presentation of sarcoidosis or an atypical granulomatous disease.13,14 CG may be classified into 3 types on the basis of the severity of the disease: simplex, superficial suppurative,
144 Lea˜ o et al
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY February 2003
Gram-negative microorganisms, played a role in the clearance of signs and symptoms. In conclusion, the present report details the clinical and histopathologic features of CG in a patient coincidentally found to have HIV infection. REFERENCES
Fig 4. Complete remission of the lesion.
and deep suppurative. The last 2 types represent a stage in which there is bacterial infection, clinically characterized by increased inflammation, suppuration, and ulceration of the lip.3 The deep suppurative type of CG has also been termed cheilitis apostematosa or myxadenitis labialis, whereas the superficial suppurative has also been termed Baelz’s disease.5 The histopathologic findings of CG are nonspecific but include local chronic sialadenitis and ductal dilatation. Dysplastic epithelial changes may occasionally occur,15 but, although associated carcinoma of the lower lip has been reported, CG is still considered to be a benign disorder that should be managed by conservative means.3,15 There are no detailed randomized studies of the treatment of CG. Surgery—for example, vermilionectomy— has been suggested to be effective. However, albeit rarely, mucoceles can occur after surgery.3,16 This patient, however, did not require vermilionectomy because the lesion fully resolved after 5 months of HAART and systemic antibacterials, despite the CD4⫹ T-cell counts only increasing marginally. The reason for the remission is unclear, but CG has been associated with bacterial infection.7 It is thus possible that sulfadiazine, being effective against Gram-positive and
1. Volkman RV. Einige falle von cheilitis glandularis apostematosa. Arch Pathol Anat 1870;50:142-4. 2. Fonseca A, Souza EM. Dermatologia Clı´nica. Rio de Janeiro: Guanabara Koogan; 1984. p. 584. 3. Rogers RS 3rd, Bekic M. Diseases of the lips. Semin Cutan Med Surg 1997;16:328-36. 4. Winchester L, Scully C, Prime SS, Eveson JW. Cheilitis glandularis: a case affecting the upper lip. Oral Surg Oral Med Oral Pathol 1986;62:654-6. 5. Weir TW, Johnson WC. Cheilitis glandularis. J Oral Med 1971; 103:433-7. 6. Yacobi R, Brown DA. Cheilitis glandularis. J Am Dent Assoc 1989;118:317-8. 7. Doku HC. Cheilitis glandularis. Oral Surg Oral Med Oral Pathol 1965;20:563-1. 8. Everett FG, Holder D. Cheilitis glandularis apostematosa. Oral Surg Oral Med Oral Pathol 1955;8:405-13. 9. Rada DC. Cheilitis glandularis: a disorder of ductal ectasia. J Dermatol Surg Oncol 1985;11:372-5. 10. Woodburne AR, Philpott OS. Cheilitis glandularis: a manifestation of emotional disturbance. Arch Dermatol Syph 1950;62: 820-8. 11. Lederman DA. Suppurative stomatitis glandularis. Oral Surg Oral Med Oral Pathol 1994;78:319-22. 12. Williams HK, Williams DM. Persistent sialadenitis of the minor glands: stomatitis glandularis. Br J Oral Maxillofac Surg 1989; 27:212-6. 13. Stuller CB. Cheilitis glandularis. Oral Surg Oral Med Oral Pathol 1982;53:602-5. 14. Scully CM, Bagan J, Eiser D, Porter SR, Rogers RS. Dermatology of the lips. Oxford: Isis Medical Media; 2000. p. 81-9. 15. Michalowski R. Cheilitis glandularis, heterotropic salivary glands and squamous cell carcinoma of the lip. Br J Dermatol 1962;74:445-59. 16. Shah JS, Shah SG, Kubavat HJ, Dayal PK. Cheilitis glandularis. J Pierre Fauchard Acad 1992;6:103-6. Reprint requests: Jair Carneiro Lea˜ o, BDS, MSc, PhD Departamento de Clı´nica e Odontologia Preventiva Universidade Federal de Pernambuco Av. Prof. Moraes Rego, 1235 Recife, PE Brazil CEP 50670-901 [email protected]