MELKERSSON-ROSENTHAL SYNDROME AND CROHN S DISEASE
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1 British Journal of Oral Surgery (1980) 18, The British Association of Oral Surgeons OOO7-117X/80/ $02.00 MELKERSSON-ROSENTHAL SYNDROME AND CROHN S DISEASE N. WORSAAE,~* K. C. CHRISTENSEN,2 S. BONDmEN and S. JARNuM~ r Department of Oral Medicine and Oral Surgery and 2 Department P, Division of Gastroenterology, University Hospital (Rigshospitalet), 9, Blegdamsvej, DK-2100 Copenhagen 0, Denmark Summary. Identical clinical and histopathological features of the oro-facial swellings in Melkersson- Rosenthal syndrome (M.R.S.) and Crohn s disease (C.D.) exist. In order to disclose a possible relation between these two granulomatous diseases and to evaluate the necessity of extensive screening for CD. in cases of M.R.S., 16 patients with complete or abortive forms of M.R.S. were examined. However, no clinical, radiological or biochemical findings indicated such a relationship. It is concluded that in patients with M.R.S. extensive examinations for C.D. are not justified in absence of associated gastrointestinal symptoms. Introduction In Melkersson-Rosenthal syndrome (M.R.S.) intermittent or persistent oro-facial swelling constitutes a prominent clinical feature, in some oligosymptomatic cases described as cheilitis granulomatosa of Miescher (C.G.). Facial paralysis and plicated tongue occur in only about one third of the patients suffering from this disorder (Hornstein, 1973). The striking resemblance, clinically as well as microscopically, between the swellings seen in M.R.S. and the oedematous, diffuse swellings of the lips, buccal mucosa, palate and gingiva occasionally observed in patients with Crohn s disease (C.D.) has been emphasised previously (Bernstein & McDonald, 1978; Chisholm et al., 1978; Tyldesley, 1979; Ward-Booth, 1979) and a possible relationship between the two diseases has been proposed (Kint et al., 1977; Tiindury, 1977; Tyldesley, 1979). In C.D. oral lesions antedating gastro-intestinal symptoms up to several years (Bishop et al., 1972; Varley, 1972; Carr, 1974; Tyldesley, 1979) and C.D. diagnosed on the basis of oral lesions alone (Varley, 1972; Taylor & Smith, 1975; Tyldesley, 1979) have been reported. Recently C.G.-like changes have been reported preceding (Carr, 1974; Tbndury, 1977; Tyldesley, 1979) and following (Kint, 1977; Tondury, 1977) gastro-intestinal involvement of C.D. In order to demonstrate a possible relationship between M.R.S. and C.D. and to evaluate the necessity of extensive screening for C.D. in patients with M.R.S., 16 patients known to be suffering from M.R.S.C.G. were examined. Investigations were carried out in order to disclose possible early gastrointestinal involvement of C.D. and signs of sarcoidosis (Boeck s sarcoid, B.S.) which histopathologically may show identical changes. Material and methods Sixteen patients (eight females, eight males) were examined. The median age was 41 years with a range from 18 to 81 years. All patients fulfilled the diagnostic criteria (Received 11 October 1979; accepted 28 January 1980) * Reprint request to: N. Worsaae, D.D.s., Department of Oral Medicine and Oral Surgery, University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen 0, Denmark. 254
2 MELKERSSON-ROSENTHAL SYNDROME AND CROHN S DISEASE 255 stipulated for M.R.S. in the present study: permanent swelling of labial and/or buccal mucosa and presence of non-caseating epithelioid cell granulomas. Fissured tongue and facial paralysis were not considered obligatory, and therefore C.G. was accepted as an oligosymptomatic form of M.R.S. The duration of symptoms related to M.R.S. ranged from four months to 39 years, with a median of four years. All 16 patients showed persistent enlargement of one or both lips (Fig. 1). Swelling of the buccal mucosa (Fig. 2), palate, gingiva and sublingual glands were inconstant features. Relapsing facial nerve paralysis had occurred in two patients. Twelve of the patients had fissured tongue, five with only moderate changes. Two patients presented all three components of the syndrome. None of the 16 patients presented either the longitudinal, hyperplastic folds in the buccal grooves or recurrent oral ulcerations which have been reported in cases of CD. of the mouth (Bernstein & McDonald, 1978). FIG. 1 (left). Permanent swelling of the lip in a patient with M.R.S., 24 years after onset of disease. FIG. 2 (right). Oedematous changes of left buccal mucosa in a patient with M.R.S. showing the characteristic lobulated pattern. Histopathological examination of biopsies obtained from the lips and in one case from the palate showed non-caseating granulomas (Figs 3 & 4) as well as para- and perivascular mononuclear infiltrations in all cases. Multinucleated giant cells, dilated lymph vessels, and oedema were additional characteristic findings in the majority of the specimens. The patients were investigated clinically, biochemically, and radiologically in order to reveal changes justifying a diagnosis of C.D. or B.S. The criteria used for C.D. and B.S. were those previously established (Hylander et al., 1976; Mitchell et al., 1977). Crohn s disease Results None of the 16 patients gave a history resembling C.D. Three patients had had gastrointestinal symptoms due to an acute attack of cholecystitis, spastic colitis (normal barium enema), and diarrhoea of unknown origin (normal extensive gastrointestinal investigations).
3 256 BRITISH JOURNAL OF ORAL SURGERY FIG. 3. Photom icrograph of labial biopsy speciman from a patient with M.R.S. I showing the char,acteristic p2 bra- and perivascular mononuclear infiltrations and granulomatous i involvement. (H&E, x 50.) FIG. 4. Higher magnification of granulomas framed in Fig. 3 showing peripheral lymphocyte w3r egation and epithelioid cells centrally. A multinucleated giant cell of the Langl hans type is indicated by arrow. (H&E, x 110.)
4 MELKERSSON-ROSENTHAL SYNDROME AND CROHN S DISEASE 257 Proctoscopy and histological examination of rectal biopsies showed normal findings, except for one case with melanosis. Biochemically, no patterns indicating inflammatory activities were observed in the investigation of haemoglobin, erythrocyte sedimentation rate, albumin, orosomucoid, transferrin, and iron in the blood. Radiologically, no abnormal changes of the small intestine and colon were found in any of the patients. Examination of the oesophagus in 12 of the patients and of the stomach in 15 of the patients revealed no abnormal findings. Sarcoidosis None of the patients gave a history suggesting B.S., and a general physical examination showed no lymphadenopathy. Biochemically, no abnormal serum concentrations of calcium, creatinine, alkaline phosphatase, and alaninaminotransferase were found. The immunoglobulin patterns in serum showed no specific alterations and no depression of Cl-esterase inhibitor values was observed. Radiologically, examinations of the right hand and of the chest showed no sign of B.S. in any of the patients. One patient had minor changes following a pleuritis. She had never had any pulmonary symptoms and at the time of investigation, a positive Mantoux was found. Discussion The criteria given for C.D. and B.S. were not fulfilled by any of the 16 patients examined. The abnormal findings recorded among the patients did not reveal disorders known particularly to be associated with either C.D. or B.S. No general biochemical or radiological changes upon which a possible mutual relationship could be based were recorded. In particular, no biochemical response to the inflammatory activity of the oral tissues were recorded, a feature which also could be suspected in cases of C.D. of the mouth without gastrointestinal involvement. The conclusion of the present study are that the occasional clinical similarities between the oral lesions of C.D. and M.R.S. merely reflect the identical underlying granulomatous involvement of the oral tissues rather than a common aetiologic or pathogenetic factor. Therefore, the presence of diffuse, oedematous, recurrent or persistent swellings in patients with M.R.S./C.G. do not seem to justify extensive screening for C.D. or B.S. in the absence of associated gastrointestinal or pulmonary symptoms. References Bernstein, M. L. & McDonald, J. S. (1978). Oral lesions in Crohn s disease: Report of two cases and update of the literature. Oral Surgery, Oral Medicine and Oral Pathology, 46, 234. Bishop, R. P., Brewster, A. C. & Antonioli, D. A. (1972). Crohn s disease of the mouth. Gastroenterology, 62, 302. Carr, D. (1974). Granulomatous cheilitis in Crohn s disease. British Medical Journal, 4, 636. Chisholm, D. M., Ferguson, M. M., Jones, J. H. & Mason, D. K. (1978). In D. M. Chisholm (editor), Introduction to Oral Medicine, p. 45. London, Philadelphia & Toronto: Saunders. Hornstein, 0. P. (1973). Melkersson-Rosenthal syndrome. A neuro-muco-cutaneous disease of complex origin. Current Problems of Dermatology, 5, 117. Hylander, E., Hansen, N. E., Karle, H. & Jarnum, S. (1976). Serum lysozyme in Crohn s disease and ulcerative colitis. Scandinavian Journal of Gastroenterology, 11, 213. Kint, A., Brauwere, D. de, Weert, J. de & Hendrickx, R. (1977). Cheilitis granulomatosa und Crohnsche Krankheit. Hautarzt, 28, 319.
5 258 BRITISH JOURNAL OF ORAL SURGERY Mitchell, D. N., Scadding, J. G., Heard, B. E. & Hinson, K. F. W. (1977). Sarcoidosis: histopathological definition and clinical diagnosis. Journal of Clinical Pathology, 30, 395. Taylor, V. E. & Smith, C. J. (1975). Oral manifestations of Crohn s disease without demonstrable gastro-intestinal lesions. Oral Surgery, Oral Medicine and Oral Pathology, 39, 58. Tyldesley, W. R. (1979). Oral Crohn s disease and related conditions. British Journal of Oral Surgery, 17, 1. Tiindury, G. D. (1977). Cheilitis granulomatosa und Morbus Crohn. Praxis, 66,792. Varley, E. W. B. (1972). Crohn s disease of the mouth. Oral Surgery, Oral Medicine and Oral Pathology, 33, 570. Ward-Booth, R. P. (1979). Hereditary angio-edema. Diagnosis and management. British Dental Journal, 146, 211.
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