ARTICLE
Crohn's disease (CD) is an inflammatory condition of unknown etiology
characterized by granulomatous inflammation primarily of the gastrointestinal
tract which may involve areas from the mouth to the anus [1]. In the majority
of cases, abdominal symptoms and weight loss are the initial manifestations
that lead to a correct diagnosis [2]. This report describes the unusual
presentation of a patient with extensive, but nearly asymptomatic gastrointestinal
involvement, in whom oral inflammatory changes were the clue for the diagnosis
of CD.
Since aphthous or aphthous-like lesions are often treated without a
definite diagnosis, we emphasize the need to consider an underlying systemic
illness in the differential diagnosis of recurrent inflammatory disease
of the oral cavity.
Case report
A 20-year-old white male was referred with recurrent, painful, intraoral
lesions of two months duration. Despite administration of erythromycin
for two weeks and use of a mouth rinse containing tetracycline and hydrocortisone,
the lesions persisted and progressed. Apart from a severe loss in body
weight (7 kg which represents 11% of total body weight within a time period
of six months) which was ascribed to malnutrition due to oral pain and
dysphagia, the patient presented no other signs of systemic disease.
Clinical examination of the oral cavity revealed multiple, pinhead-sized
pustules, partly arranged in a linear distribution in the vestibulum and
more disseminated on the hard and soft palate (Figs.
1 and 2);
in addition, there were 1-2 mm sharply demarcated, punched-out erosions
and superficial ulcerations surrounded by an inflammatory halo. Following
the time course of these lesions, pustules appeared in crops, rupturing
within hours and transforming into the ulcers described. Thus, the patient
presented with a changing daily picture, at times with a predominance
of pustules and at times with linear aphthous ulceration.
Routine laboratory examinations showed a slightly
elevated erythrocyte sedimentation rate (35/80-Westergren) and elevated
acute phase reactants. Cultures for bacteria and fungi obtained from the
oral mucosa were negative as were direct immunofluorescence tests for
Herpes simplex virus type I and II antigens. Tests for human immunodeficiency
virus were negative, and a study of peripheral CD4+ and CD8+
lymphocyte levels yielded normal results. Two biopsies from the oral mucosa
were performed at different stages of the disease. The first biopsy showed
the epithelium with spongiosis and the papillary dermis with edema. In
the dermis, a dense perivascular and interstitial infiltrate with plasma
cells, numerous neutrophils and few eosinophils was present. The second
biopsy obtained from the vestibular mucosa revealed a superficial erosion
with an underlying dense, mononuclear infiltrate containing lymphocytes,
plasma cells and few eosinophils. Small, noncaseating granulomas composed
of epitheloid cells and multinucleated giant cells revealed no evidence
of microbial agents in the PAS, Gram's and Ziehl-Neelsen stains and thus
suggested Crohn's disease (Fig.
3). Immunofluorescence showed only mild perivascular fibrin deposits.
Colonoscopy was performed and demonstrated active terminal ileitis and
inflammation of the ileocecal valve; minor inflammation was present in
the ascending and descending colon. Since dysphagia was one of the patient's
most prominent symptoms, gastrointestinal endoscopy was performed showing
mucosal involvement in the form of tiny pustules and fibrin-coated erosions
reaching from the esophagus to the duodenum (Fig.
4). The diagnosis of active CD was confirmed by the typical histologic
features in biopsies obtained from different areas (esophagus, antrum
and fundus ventriculi, duodenum, ileum, cecum, colon and rectum) of the
gastrointestinal tract (Fig. 5).
No sign of infectious disease, especially candidiasis, could be found.
The patient was treated with 50 mg of prednisone daily resulting in
a 50% resolution of the oral lesions after only 4 days. At the time of
discharge, 10 days following the initiation of prednisone, the lesions
had completely cleared even after reduction of the dosage to 25 mg daily.
Steroids were tapered and discontinued after five months. The patient
is now well with medication consisting of 1,000 mg of sulfasalazine, three
times a day.
Discussion
Oral lesions of Crohn's disease (CD) were first described by Dudeney
[3] in 1969. Since then a number of cases have been reported [4-6], but
oral involvement in CD still remains an unusual manifestation and is therefore
often misdiagnosed. Although CD primarily affects the gastrointestinal
tract, the incidence of oral involvement ranges from 4 to 14% with a greater
prevalence in adolescents and young adult males [7]. Although oral lesions
are not a predominant clinical sign in the course of CD, they often precede
intestinal symptoms in a substantial number of patients (range of 30-60%)
[8, 9].
Intestinal symptoms are usually the first clue
to diagnosis of CD, but in our case the painful oral erosions and pustules
resistant to topical treatment masked the gastrointestinal symptoms. Loss
in body weight and dysphagia should have been an early clue to the correct
diagnosis, but were understandably attributed to the patient's inability
to eat because of oral pain. In patients presenting with recurrent inflammatory
changes of the oral cavity, the manifestations of CD should always be
taken into account for the differential diagnosis. This includes 1) viral
etiology such as gingivostomatitis herpetica or disseminated herpetic
infection in immunocompromised patients and Coxsackie virus infection
(herpangina, hand-foot-and-mouth-disease); 2) chronic recurrent herpetiform
aphthae; 3) erosive candidiasis; 4) fixed drug eruption; 5) bullous dermatosis
such as cicatricial pemphigoid and 6) oral manifestations of myelodysplastic
diseases. In order to rule out oral involvement in CD, a diagnostic biopsy
of pustular and small ulcerative lesions in otherwise asymptomatic patients
should be the rule. A chronic inflammatory infiltrate consisting of mononuclear
cells, giant Langerhans cells and epitheloid cells in the lamina propria
and noncaseating granulomas are highly suggestive of CD and resemble microscopic
lesions found elsewhere in the alimentary tract [10].
The specific oral manifestations of CD described here should not be
confused with pyostomatitis vegetans (PV) which has been described as
a marker for inflammatory bowel disease [11]. PV mainly affects patients
with ulcerative colitis, but an association with CD has been observed
[12]. This rare condition is characterized by pustular oral lesions which
become vegetative and coalesce to form so-called "snail track" patterns
[13]. Histopathologically, the difference mainly consists of the lack
of sarcoidal granulomas in PV [14].
In reviewing the literature, we have found an underrepresentation of
descriptions of oral CD in the dermatological literature. We conclude
that this severe gastrointestinal disorder should always be taken into
consideration in the differential diagnosis of oral pustular, ulcerative
lesions, especially when presenting with deep, granulomatous-appearing
ulcers in a linear or herpetiform distribution and developing in the vestibulum
oris. These clinical features are described as typical of oral CD.
REFERENCES
1. Dayal Y, DeLellis RA. The gastrointestinal tract. In: Cotran RS, Kumar
V, Robbins SL, eds. Robbins pathologic basis of disease, 4th ed.
Philadelphia: WB Saunders, 1989: 827-909.
2. Podolsky DK. Inflammatory bowel disease: part I. N Engl J Med
1991; 325: 928-37.
3. Dudeney TP, Todd IP. Crohn's disease of the mouth. Proc Roy Soc
Med 1969; 62 (12): 1237-8.
4. Halme L, Meurman JH, Laine P, et al. Oral findings in patients
with active or inactive Crohn's disease. Oral Surg Oral Med Oral Pathol
1993; 76: 175-81.
5. Weiss JS, Gupta AK, Regezi J, Rasmussen JE. Oral ulcers and cobblestone
plaques. Oral Crohn's disease. Arch Dermatol 1991; 127 (6): 889-92.
6. Field EA, Tyldesley WR. Oral Crohn's disease revisited a 10-year-review.
Br J Oral Maxillofac Surg 1989; 27 (2): 114-23.
7. Basu MK, Asquith P. Oral manifestations of inflammatory bowel disease.
J Clin Gastroenterol 1980; 9: 307-21.
8. Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn's disease.
J Clin Gastroenterol 1991; 13 (1): 29-37.
9. Neville BW, et al. Oral and maxillofacial pathology. Saunders,1995:
620.
10. Williams AJK, Wray D, Ferguson A. The clinical entity of orofacial
Crohn's disease. Q J Med 1991; 289: 451-8.
11. Van Hale HM, Rogers RS, Zone JJ, Greipp PR. Pyostomatitis vegetans:
a reactive marker for inflammatory disease of the gut. Arch Dermatol
1985; 121: 94-8.
12. Ballo FS, Camisa C, Allen CM. Pyostomatitis vegetans: report of
a case and review of the literature. J Am Acad Dermatol 1989; 21:
381-7.
13. Neville BW, Smith JE, Maize JC, et al. Pyostomatitis vegetans.
Am J Dermatopathol 1985; 7 (1): 69-77.
14. Ficcara G, Cicchi P, Amorosi A, et al. Oral Crohn's disease
and pyostomatitis vegetans. Oral Surg Oral Med Oral Pathol 1993;
75: 220-4.
|
Version imprimable
