W. R. TYLDESLEY, D.D.s., PH.D., F.D.S.R.C.S.

Transcription

1 British Journal of Oral Surgery 17 (I 979~80), 1-9 ORAL CROHN S DISEASE AND RELATED CONDITIONS School W. R. TYLDESLEY, D.D.s., PH.D., F.D.S.R.C.S. of Dental Surger,y, Pembroke Place, P.O. Box 147, Liverpool, t.69 3BX, U.K. Summary. It has become widely recognised that oral lesions may occur in patients with Crohn s disease of the lower gastro-intestinal tract. Patients have also been described with oral lesions of this kind unassociated with gut lesions. The purpose of this paper is to describe the clinical presentation of seven such patients. The resemblance of their lesions to those of the condition known as chronic granulomatous cheilitis is pointed out. The association between the oral lesions and those of the lower gut is discussed and it is reported that in one patient acute toxic dilatation of the colon due to Crohn s disease followed a period in which oral lesions only were recognised. Introduction Crohn s disease was first described in In that year Crohn, Ginzburg and Oppenheimer presented their observations of patients with a form of regional ileitis which they were able to differentiate from other non-specific inflammatory conditions of the bowel and, in particular, from the tuberculous infections with which it had probably been previously confused. Some patients whose histories had been recorded before 1932 were probably suffering from Crohn s disease although there can be no certainty about this. A number of patients with suggestive histories are reviewed by Kyle (1972) who is able to give examples of possible cases dating from the year 1769 onwards. Following the original description of a disease with lesions affecting only the ileum it has been accepted that lesions of a similar type may affect other parts of the gastro-intestinal tract and the term Crohn s disease is applied to these also. The aetiology of Crohn s disease is not known and, largely for this reason, the eponymous nomenclature is maintained. Recent speculations include the suggestion that the disease may result from an immune reaction, possibly precipitated by the antigens of gut bacteria (Basu, 1976). However, a number of well-defined changes are seen in a patient suffering from the condition. Granulomatous lesions occur in the affected gut and a particularly transmural inflammatory process occurs throughout the layers of the affected organ. Characteristically the granulomatous areas contain non-caseating tuberculoid structures including foreign body type giant cells but this histology is not invariable. There is enlargement of the associated lymph nodes, with lymphatic obstruction and oedema of the affected organ. Ulceration of the gut mucosa may be secondary to these changes and fistulae of various kinds may follow. The most common symptoms complained of by the patients are recorded by Kyle as being abdominal pain (85 per cent), diarrhoea (62 per cent), weight loss (50 per cent) and vomiting (48 per cent). Other symptoms such as fever and rectal bleeding are present in a small percentage of patients. The patients are generally young at the first appearance of the symptoms, the risk of developing Crohn s disease being highest in the year age group. The incidence of the disease seems to be widely variable in different parts of the world and the sex distribution also varies according to the geographical area surveyed. (Received 19 April 1978; accepted 25 May 1978)

2 2 13RITISH JOURNAL OF ORAL SURGERY Unfortunately specific laboratory tests for Crohn s disease do not as yet exist. This is again to some extent a reflection of the lack of knowledge as to the aetiology of the condition. Immunological changes have been noted in affected patients and may eventually become the basis of diagnostic tests (Basu rt al., 1975). At the present time, however, the diagnosis is essentially a clinical one reinforced by radiographic studies and by histological study of tissue removed at biopsy or operation. However, malabsorption may be an early consequence of gastro-intestinal disease and a lowering of the serum folate. iron or B12 levels may give an early indication of the existence of such pathology. These changes may be of great importance in the investigation of patients with suspect oral lesions as giving the earliest possible signs of gastrointestinal changes. Oral lesions in Crohn s disease Oral lesions in Crohn s disease, histologically resembling those of the lower gut, have been described in several papers which have appeared since the initial description by Dudeney and Todd in Following this paper and others (including those by Issa, 1971; Schiller et al., 1971; Ellis & Truelove, 1972; Stankler et al., 1972; Verbov, I973 and Basu et al., 1975) a reasonably clear idea of the oral lesions has been gained. It is generally accepted that a significant proportion of patients with Crohn s disease suffer from oral ulceration resembling aphthous ulceration. This may or may not be a directly related phenomenon. The characteristic changes in the oral cavity appear to be a thickening and oedema of the buccal mucosa, the abnormal tissue being thrown into folds. These corrugations may include ulcers lying deep in the tissue folds or may become traumatised with more superficial ulceration. Individual rather proliferative granulomas may occur, and may be mistaken for early neoplasms - these have been described by several authors as resembling denture granulomas. Angular cheilitis, swollen lips and cheeks, and fissured lips have also been described in various patients. In the majority of the cases in which biopsies have been taken from the affected oral mucosa, granulomatous areas of a tuberculoid type similar to those described as characteristic of Crohn s disease of the gut have been present. In one or two cases, however, this characteristic histology has not been demonstrated. This is in accord with the uncertain nature of the histological appearances in the lower gut. Only two reports have appeared in which the oral lesions of Crohn s disease have been described in the absence of gastro-intestinal lesions. Varley in 1972 described three patients, one of whom presented with typical buccal lesions said to resemble denture granulomas. No intestinal symptoms were reported in this patient. In their paper of 1975, Taylor and Smith gave a documented case report of an l&year-old male patient in which an oral lesion was again described as resembling a denture induced hyperplasia. The lesion was ulcerated and painful. The histology of the lesion was similar to that of a granuloma in Crohn s disease. Contrast radiography, sigmoidoacopy and tests for nutritional status all proved normal. It was concluded that this patient represented a case of Crohn s disease restricted to the mouth only. Related oral Iesions The oral lesions to be considered in a comparative study of oral Crohn s disease include those of tuberculosis, sarcoid and granulomatous cheilitis.

3 ORAL CROHN S DISEASE AND RELATED CONDITIONS 3 1. Tuberculosis occasionally arises either as a primary or secondary lesion of the oral mucosa and a number of presentations have been described. Although the range of these is wide no lesions have been reported which resemble the corrugated oedematous buccal mucosa seen in Crohn s disease. However, the absolute elimination of tuberculosis as a possible diagnosis in any case of tuberculoid granuloma in the mouth is not easy and any patient with such a presenting lesion should be investigated with this possibility in mind. 2. Lesions of sarcoid occasionally occur in and around the oral tissues, the lip being the most commonly described site, Although the histology of such a lesion is similar to that described in Crohn s disease the clinical description is of a solitary mass with local oedema only. Again the characteristic corrugated appearance of the buccal mucosa in Crohn s disease has not been described as associated with sarcoid. Although it is clearly possible for isolated lesions of sarcoid to occur within the oral tissue it is generally accepted that a definitive diagnosis would depend on the presence of lesions in the lung or other organs. The Kveim test, positive in cases of sarcoid, seems to depend for its absolute specificity on the exact nature of the antigen available. In particular there are varying reports of a positive Kveim reaction in cases of Crohn s disease. 3. Chronic Granulomatous Cheilitis is a condition which was described by Miescher (1945). The main features described are oedema of the lips together with granulomatous lesions of the labial and buccal mucosa. Tuberculoid structures are found in these granulomas. It is the author s belief that this condition is probably identical with that of the patients described in the present paper. 4. In a number of publications, and in particular in the extremely authorative work by Gorlin et al. (1976) the Melkersson-Rosenthal syndrome is considered as being of a similar type to the conditions at present under discussion. A single established case of this rare syndrome has been investigated by the present author - in this patient the syndrome was present in its most fully developed form. The patient, a female aged 47 years, presented with a history of recurrent facial swelling involving the cheeks and lips, and of an inconstant site. This swelling was accompanied by temporal headaches resembling those of migraine. There was a history of transient seventh nerve paralysis which had affected both the left and the right sides separately. The patient had also a very deep midline fissure of the tongue. No granulomatous lesion of any kind was seen and, in general, it was felt that the clinical presentation in this patient was quite different from that in the patients with Crohn s disease. It need hardly be said, however, that no explanation is offered by the author regarding this strange syndrome. Case reports Two patients (1, 2, male, aged 20 and 22 years respectively) with Crohn s disease of the lower gut have been diagnosed following histological examination of oral lesions. These lesions consisted in each case of thickening and fissuring of the buccal mucosa (Fig. l), and the presence of typical tuberculoid granulomas (Fig. 2). Although the oral lesions were in these two cases responsible for the diagnosis of the condition it should not be assumed that they represented the earliest manifestations of the disease. In both cases suggestive abdominal symptoms were present and contrast radiography showed the typical appearance of Crohn s disease. One of the patients had also suffered a considerable weight loss which had remained undiagnosed. It

4 BR171SH JOURNAI. OF ORAL. SIJK<;l:K\r FIG. I Corrugated appearance of buccal mucosa - patient I. FIG. 2. Non-caseating tuberculoid structure of buccal lesion in patient 2 (medium power). is, therefore, likely that the lower gut lesions of Crohn s disease were present altha ugh undiagnosed before the onset of the oral lesions. These cases of gastro-intestinal Crohn s disease with oral lesions show few dissimilarities from those previously recorded and should perhaps be considered as typical of the condition when the oral tissues are involved.

5 ORAL CROHN S DISEASE AND RELATED CONDITIONS 5 Oral lesions only Six patients have been observed with lesions, resembling those of Crohn s disease, apparently restricted entirely to the oral and perioral tissues. Details of these patients are given in Table I. Table I Details of patients with oral lesions only Patient Sex Age of onset Swollen lip Angular cheilitis Buccal lesions Palpable nodes 3 F IO 4 F IO 5 F 12 6 M 11 7 M 16 8 M The patients have been observed over a period of five years (patients 3, 4, 5) four years (6) and two years (7, 8) and from these observations a compound picture of the condition has been built up. It will be seen that three patients were male and three female and that the age range at the onset of symptoms was from 10 to 16 years. In five cases (3 to 7) the initial complaint was of swelling of the lip or lips (Figs 3 and FIG. 3 (top left). Swollen upper lip, patient 7. FIG. 4 (top right). Swollen lower lip, patient 3. FIG. 5 (bottom left). Swollen and fissured lower lip with angular cheilitis, patient 4.

6 6 BRITISH JOURNAL. OF ORAL SURGERY 4). All six presented with granulomatous lesions of the buccal mucosa closely resembling those illustrated in Fig. 1 and patients 3 to 7 were found to have enlarged and indurated submandibular lymph nodes. In each case angular cheilitis had been troublesome (Fig. 5) as had fissuring of the lips. In patients 3-7 the buccal lesions, although evident, were not initially painful. In patient 5 the buccal granulomatous lesions extended on to the gingivae but again these proved to be symptom-free, The clinical picture presented by patient 8 was somewhat different in that the initial complaint was of ulcerated and secondarily traumatised buccal lesions which caused considerable discomfort. Swelling of the lower lip of a minor degree occurred only some 12 months after the established presence of the buccal lesions. Angular cheilitis was, however, present. It will be seen by reference to Table I that marked submandibular nodes were not present in this patient, All six patients in this group were sub.jected to contrast radiography of the gastrointestinal tract without abnormality being shown. Six-monthly checks on the nutritional status have been carried out by taking a full range of haematological values. These have also proved normal except in the case of patient 4 who has persistently shown an iron deficiency. The precise aetiology of this remained obscure, repeated tests for occult blood having proved negative. No evidence of active tubercular infection has been found and in five of the cases a Kveim test proved negative. In case 7, however, the Kveim reaction was positive and remained so on repeat. It was not considered that this constituted evidence of sarcoid in view of the clinical presentation and of the known non-specificity of the test. In this case, as in the other patients in this group, the chest film showed no lung pathology. The eventual prognosis of the oral lesions is unknown. It is possible to say, however, from the observation of patients 3-6 over a period of five years that in general the buccal lesions and the oedema of the lips have shown slow resolution from the time of initial diagnosis or shortly afterwards and that this seems to have been little influenced by attempts at treatment. Patients 7 and 8 have been under observation for a relatively short period of time and it is not possible to make accurate comments regarding progression of their disease. Photography has been of great help in comparative assessment of facial swelling in these patients. Oral lesions preceding gut lesions. A further patient (9) presented with a history similar to that of patients 338. This female patient, aged 27 years, was complaining of intermittent swelling of the upper and lower lips, present for approximately one year. This had been preceded by an episode of ulceration of the buccal mucosa. On initial examination the patient was seen to have swelling of the lips resembling that described previously. Irregularity of the buccal mucosa, angular cheilitis and a single palpable submandibular lymph node were noted. A biopsy of the buccal irregularity was reported as showing only non-specific inflammatory changes. Haematology values were normal apart from a slightly depressed serum folate (2.7 pg/l) and an elevated E.S.R. (35 mm/hr Wintrobe). In spite of the equivocal oral findings, Crohn s disease was considered as a possible diagnosis and gastro-intestinal studies were performed. Clinically and radiographically no abnormality was found with the exception of an anal tag which was excised for biopsy purposes. This showed non-specific chronic inflammatory changes as did a rectal mucosal biopsy. The patient was observed for approximately 18 months during which time no gastro-intestinal symptoms of any kind were complained of. A repeat barium meal

7 ORAL CROHN S DISEASE AND RELATED CONDITIONS 7 and follow through (at 16 months) were reported as normal and repeated haematological tests showed no marked variation in the mild folate deficiency previously reported. Following this symptom-free period abdominal discomfort rapidly developed and the patient was admitted to hospital complaining of acute abdominal pain and sudden weight loss. Laparotomy disclosed an acute megacolon which was resected and showed characteristic changes of Crohn s disease throughout its length. The patient did not recover from complications following this operation. Treatment Treatment of generalised Crohn s disease depends mainly on the use of anti-inflammatory agents, corticosteroids, sulphonamides and immuno-suppressive agents. Most commonly an attempt is made to maintain a patient with active gut lesions on minimal dcsages of prednisolone, varying the dose according to the severity of the symptoms. It has generally been noted that in those patients with oral lesions associated with active gastro-intestinal disease the oral lesions vary in severity in approximate parallel with the symptoms arising from the gut lesions. This is so both in respect of spontaneous variation in activity and also the response to therapy. This general observation has been confirmed in the case of patients 1 and 2 whose ulcerated and painful oral lesions have in each case responded to the use of varying doses of oral prednisolone in much the same way as the gastro-intestinal symptoms. In both patients minimal maintenance dosages of prednisolone are used and oral lesions are a problem only at the time of exacerbation of the abdominal symptoms. Most therapeutic rcgimes used in the control of Crohn s disease have considerable disadvantages, and thus careful consideration must be given to their adoption for local lesions such as those in the mouth. Experience in the cases of patients I, 2 and 6 would suggest that systemic prednisolone is effective in reducing symptoms arising from painful ulcerated buccal granulomatous lesions but is ineffective in the reduction of the oedema of the lips (3, 4 and 7). Jntra-lesional triamcinolone has been suggested as a suitable treatment for the oedema of the lips (Cerimele & Serri, 1965) but in the author s hands, using varying concentrations of the steroid, this has not proved successful. In view of the possibility that the oedematous swelling is due to blockage of the lymph drainage to the area it is not surprising that local infiltrations are not successful. The angular cheilitis associated with the oral lesions has uniformly responded to the use of 1 per cent Hydrocortisone ointment, reinforced initially by the use of a suitable antibiotic or anti-fungal cream, depending on the results of bacteriological examination. This is in accord with the response of anal fissures to a similar rcgime. Antiseptic mouthwashes have been used to reduce the pain and soreness of ulcerated oral lesions. In view of the observation made above that in cases 3-7 the troublesome oral lesions have slowly resolved over a period of years, it might well be that the appropriate approach to treatment should be as conservative as possible. However, the pain and discomfort associated with ulcerated buccal lesions can, as in patient 8, necessitate a more aggressive approach. Discussion Three major points arise in the consideration of these cases. The first is as to whether the lesions described are in fact those of Crohn s disease as it is at present understood. In view of the close clinical and histological similarities between the oral lesions of

8 8 f3rf f fsf-1 JOURNAL. OF, OKAf SUKGEKl patients with and without established lower gut Crohn s disease it would seem that the evidence points strongly to the identity of the basic process, whatever that might be. In view also of the known nature of Crohn s disease as a process which ma) effect virtually any part of the gastro-intestinal tract it would seem that this identit? could reasonably be assumed. As has been pointed out above it would seem that the condition previously described as chronic granulomatous cheilitis may well be the same condition, clinical and histological descriptions proving identical in the two cases. These speculations will no doubt be eventually made unnecessary by the increase in knowledge of the immunopathology of Crohn s disease and the recognition of specific immunological markers. The second point of importance is that previously it has not been established whether the patient with Crohn s-like lesions restricted to the oral mucosa may develop the disease in other parts of the gastro-intestinal tract. The unfortunate chain of events described in patient 9 seems to show clearly that this can, in fact, occur. This patient was subjected to most careful investigations for the presence of lower gut lesions and was thought to be completely free of these until very shortly before the acute episode described. It should be remembered, however, that during the whole of the period under observation she had shown the mild signs of malabsorption which imply some pathology of the gastro-intestinal tract, whether or not demonstrable on endoscopy or by X-ray. This reinforces the view that tests of nutritional status may be of great importance in the observation of these patients. It is suggested therefore, that patients with lesions of the kind described (whether or not the histology is of a tuberculoid type), should have the benefit of a full gastro-intestinal contrast radiographic examination. It is also suggested that tests for nutritional status should be carried out initially and repeated at six-monthly intervals, so long as the oral lesions are evident, and possibly for some time afterwards. Further, it is suggested that any sign of abdominal discomfort or the appearance of nutritional deficiency should be considered as a warning of the possible onset of gastro-intestinal lesions even in the face of previous normal radiographic reports. A third intriguing question arises. All reports of oral lesions of the kind under discussion have been made since As has been outlined previously, Crohn s disease itself has been known only since the year 1932 although there is no firm evidence that it did not exist for an unknown past period. It is nonetheless strange that marked oral and perioral lesions with cosmetic significance should have gone unrecorded until relatively recently. Whether this is simply an expression of greater awareness and the availability of diagnostic facilities or whether it represents a true increase in the incidence of the condition is as yet impossible to tell. Acknowledgements A number of colleagues have co-operated closely in the investigation and management of these patients. Dr R. B. McConnell, Professor F. Harris and Dr R. W. Galloway have been particularly involved. References Basu, M. K. (1976). Oral manifestations of Crohn s disease: studies in the pathogenesis. Proceedings of the Royal Sociefy of Medicine, 69, 765. Basu, M. K., Asquith, P., Thompson, R. A., &Cooke, W. T. (1975). Oral manifestations of Crohn s disease. Gut, 16, 249. Cerimele, D., & Serri, F. (1965). Intra-lesional injection of triamcinolone for the treatment of cheilitis granulomatosa. Archives of Dermatology, 92, 695. Crohn, B. B., Ginzburg, L., & Oppenheimer, G. D. (1932). Regional ileitis: a pathologic and clinical entity. Journal of the American Medical Association, 99, 1323.

9 ORAL CROHN S DISEASE AND RELATED CONDITIONS 9 Dudeney, T. P., & Todd, I. P. (1969). Crohn s disease of the mouth. Proceedings of the Royal S0ciet.v of Medicine, 62, Ellis, J. P., & Truelove, S. C. (1972). Crohn s disease with mouth involvement. Proceedings of the Royal Society of Medicine, 65, Gorlin, R. J., Pindborg, J. J., & Cohen, L. (1976). Syndromes of the Head and Neck, 2nd Ed. New York: McGraw Hill. lssa, M. A. (1971). Crohn s disease of the mouth. A case report. British Dental Journal, 130, 247. Kyle, J. (1972). Crohn s Disease. London: Heinemann. Miescher. G. (1945). Uber essentielle Granulomatose Makrocheilie (Cheilitis eranulomatosa). Dermatolo&ca, 91, 57. Schiller, K. F. R., Gelding, P. L., Peebles, R. A., & Whitehead, R. (1971). Crohn s disease of the mouth and lips. Gut. 12, 864. Stankler, L., Ewen, S. W. B., & Kerr, N. W. (1972). Crohn s disease of the mouth. British Journal of Dermatology, 87, 501. Taylor, V. E., & Smith, C. J. (1975). Oral manifestations of Crohn s disease without demonstrable gastrointestinal lesions. Oral Surgery, Oral Medicine, Oral Pathology, 39, 58. Varley, E. W. B. (1972). Crohn s disease of the mouth: report of three cases. Oral Surgery, Oral Medicine, Oral Pathology, 33, 570. Verbov, J. (1973). The skin in patients with Crohn s disease and ulcerative colitis. British Journal of Dermatology, 88, 517.