Sarcoidosis Resulting in Duodenal Obstruction in an Adolescent

Abstract

Sarcoidosis is a multisystem granulomatous disorder of undetermined etiology. The hallmark characteristic of the disease is the formation of noncascating epitheloid cell granulomas at the site of involvement (1,2). Although it rarely affects the gastrointestinal tract, when it does, the stomach is the most frequent site of involvement, while small bowel sarcoidosis is extremely rare (3,4). Intestinal lesions occasionally cause symptoms due to a cicatrizing constriction of the bowel lumen secondary to the granulomatous process or external compression by involved lymph nodes (5). The resulting constriction and inflammation may result in abdominal pain, weight loss, diarrhea, and intestinal protein loss, making differentiation from small bowel Crohn's disease difficult (6-9). In a review of the medical literature, there is one reported case of duodenal obstruction (10) and six reported cases of small intestinal involvement as the major presenting feature of systemic sarcoidosis in adults (4). We present the first case of intestinal sarcoidosis in an adolescent and briefly review the literature on gastrointestinal sarcoidosis. CASE REPORT The patient was a 15-year-old black boy who was in good health prior to the sudden onset of loose stools. Two weeks later he developed proptosis. Evaluation with a computerized tomographic (CT) scan demonstrated a left lateral periorbital mass confined to the lacrimal gland (Fig. 1). Biopsies of this mass revealed noncaseating granulomas suggesting sarcoidosis. His PPD tuberculin test was negative, and the angiotensin-converting enzyme (ACE) level was 65 U/L (normal 8-52 U/L). The proptosis resolved spontaneously within 2 weeks. He then developed early satiety, nausea, and frequent postprandial emesis. His symptoms progressed in severity, resulting in a 10-lb weight loss, increasing fatigue, and generalized weakness. An upper gastrointestinal series with small bowel follow-through revealed a marked concentric narrowing of the descending duodenum, with a luminal diameter of 4 mm (Fig. 2). The terminal ileum displayed multiple nodular filling defects with mucosal irregularities suggesting lymphoid hyperplasia. He was hospitalized for nutritional rehabilitation and further diagnostic evaluation. A CT scan using intravenous and oral contrast agents showed a constricting annular lesion in the second portion of the duodenum (Fig. 3). The liver, kidney, spleen, and adrenal glands were unremarkable. The patient was evaluated with upper endoscopy, which revealed multiple aphthous lesions throughout the stomach with antral nodularity and hyperemia. The duodenal bulb was erythematous with marked narrowing of the lumen. Biopsies from the duodenum, antrum, and fundus were negative by a urease slide test (CLO; Delta West) and histologic assessment for Helicobacter pylori. Biopsies from the duodenal bulb revealed a marked increase in acute and chronic inflammatory cells, acute cryptitis, and villous blunting. The antral histology showed acute and chronic inflammatory infiltrate with multiple noncaseating granulomas (Fig. 4). Colonoscopy with ileoscopy was unremarkable with normal biopsies from the terminal ileum, cecum, sigmoid colon, and rectum. Laboratory evaluation showed the following values: hemoglobin 14.5 g/dl; erythrocyte sedimentation rate 18 mm/h; white blood cells 7,600/ml with a normal differential; total protein 7.2 g/dl; albumin 4.1 g/dl; and spot stool α1-antitrypsin 113 μg/dl (normal <54 μg/dl). He had a normal chest x-ray film. Delayed hypersensitivity skin testing did not demonstrate anergy. The patient was initially started on continuous-drip enteral alimentation and peripheral parenteral nutrition. Methylprednisolone was begun at a dose of 2 mg/kg/day in a TID dosage regimen. Within 48 h he was tolerating a regular diet with an adequate daily caloric intake. After discharge from the hospital, he continued to do well with a return to his normal weight and activities while his prednisone was slowly tapered to 20 mg every other day. Although he remained asymptomatic during follow-up, his ACE level rebounded from a normal level of 24 to 97 U/L while on every other day prednisone, prompting a return to low-dose daily prednisone therapy (10 mg QD) with subsequent normalization of his ACE level. His subsequent endoscopic and radiographic evaluations showed a persistence of the partial obstruction in the second portion of the duodenum. The noncaseating granulomas were no longer present on histology, but chronic inflammatory changes persisted along with an increased number of plasma cells in the submucosa. Follow-up stool α1-antitrypsin and ACE levels returned to normal on daily steroids, and our patient is currently symptom-free 18 months following his initial diagnosis. DISCUSSION The diagnosis in this patient was a difficult one because sarcoidosis is one of several overlapping syndromes with granulomatous formation in response to an offending agent. Infectious etiologies such as tuberculosis, leprosy, Whipple disease, and fungal infections or a malignancy such as lymphoma must be excluded. The main difficulty in establishing the diagnosis is differentiation from Crohn's disease. Both entities may present with nonspecific symptoms such as fever, fatigue, nausea, weight loss, and anorexia (1-4). Our patient's dramatic response to steroids is consistent with previous reports of patients with intestinal sarcoidosis, but would be unusual for patients with Crohn's disease (4,5,10,11). The diagnosis of duodenal obstruction secondary to sarcoid is supported by his negative PPD, elevated ACE levels, lacrimal gland involvement, and the superficial location of the mucosal histologic findings including granulomata, inflammatory changes, and villous blunting. The absence of abdominal pain, perianal disease, and fistulas in addition to the normal endoscopic and histologic findings on terminal ileum and colon, the cicatrizing nature of the duodenal obstruction, and his clinical response together argue against a diagnosis of Crohn's disease. Intestinal involvement with sarcoid is unusual. This case is especially unique when the age of the patient is considered. Patients with sarcoidosis most frequently display symptoms between the ages of 20 and 40 years (6). The youngest previously reported patient with intestinal sarcoidosis was 30 years old (3). Several patients have been reported with sarcoid involving the esophagus, stomach, small bowel, and colon. There is one previous case report of duodenal obstruction resulting from sarcoid infiltration of the duodenum (10). A review of 320 autopsy cases of sarcoidosis by Iwai et al. (12) revealed four cases with gastric involvement and eight cases with small intestinal sarcoid, accounting for ≈4% of the cases. Sarcoid involving the abdominal lymph nodes was seen in 41% of their patients. In contrast to our patient, when intestinal symptoms occur with sarcoid, they are usually the result of luminal compression by abdominal lymph nodes (10). Sarcoidosis begins with an accumulation of mononuclear inflammatory cells in the affected organ, followed by granulomata formation with macrophages, epithelioid cells, and multinucleated giant cells. The organ dysfunction results from the accumulating inflammatory cells distorting the architecture of the tissue (6). The duodenal obstruction in our patient is probably a cicatrizing constriction secondary to sarcoid involvement. This is more typically seen with granulomatous infiltration of bronchial tissue, resulting in obstructive pulmonary lesions. Fibrotic constriction is common in pulmonary disease and may result in chronic obstructive pulmonary lesions (6). The constrictive lesion in the duodenum seen in our patient is similar to the lesions reported in adults with gastric sarcoid resulting in outlet obstruction (10,11). Radiographic findings in patients with intestinal involvement include gastric ulcerations, antral narrowing, and antral deformity (4). In the patient of Stampfl et al. (10), the upper gastrointestinal series and CT scan revealed a circumferential thickening of the second portion of the duodenum with thickened mucosa and narrowing in the third portion of the duodenum, like those observed in our patient (Fig. 2 and 3). Other abdominal manifestations include hepatomegaly, abdominal lymphadenopathy and discrete hepatic nodules (13, 14). Endoscopy in a previously reported patient with duodenal obstruction showed extrinsic compression of the gastric antrum and of the second and third portions of the duodenum. Biopsies obtained following the initiation of treatment revealed intact mucosa and chronic inflammation in the lamina propria (10). In another patient with small bowel disease, mucosal biopsies revealed sarcoid-like granulomas in the submucosa with partial villous atrophy (3). Bulger et al. (9) reported a 48-year-old patient with disseminated sarcoidosis who at autopsy showed multiple granulomas in the large and small bowel associated with an increased number of lymphocytes and plasma cells in the lamina propria. Chinitz et al. (11) reported gastroscopy and histologic findings in 11 patients with symptomatic gastric sarcoid. The endoscopic appearance varied with patients having antral nodularity, gastritis, thickened gastric folds, or normal appearance. Histologically all 11 patients revealed mucosal and/or submucosal granulomata. Our patient had nodular lesions in the antrum and pylorus with superficial ulcerations in the antrum. The duodenum revealed an extrinsic compression resulting in progressive narrowing to the point of almost complete obstruction in the second portion of the duodenum (Fig. 3). The histology was remarkable for villous blunting, lymphocytic infiltration, and acute cryptitis. Noncaseating granulomas were noted in the mucosa (Fig. 4). These changes are consistent with the findings from previously published reports. Ocular lesions occur in ≈20% of patients with sarcoidosis, often involving the eye and/or the surrounding glandular structures. Uveitis is the most common ocular lesion, but the lacrimal glands are also frequently involved. While uveitis is not uncommon in Crohn's disease, lacrimal gland involvement with granulomata is not seen (6-10). ACE levels are elevated in 75% of patients with sarcoidosis and have been shown to correlate with the level of disease activity (15-17). This enzyme is produced by epithelial cells in the granulomata; serum levels reflect the total granulomatous load in the body (2). Although ACE levels are higher in infants and children, adolescents have serum levels that approximate adult values (18). Overall 80% of children with sarcoidosis have an elevated serum ACE level at the time of diagnosis. Moreover, children also demonstrate a decrease in the serum level in response to therapy (18). Other disease entities such as tuberculosis, silicosis, leprosy, berylliosis, and Gaucher disease may display increased ACE level (1,2), but it is not elevated in patients with Crohn's disease (15). Although the precise etiology of sarcoidosis is not known, several mechanisms have been proposed to explain this disorder. Sarcoidosis may result from (a) an altered immune response to an inciting agent resulting in an exaggerated T helper cell response; (b) an inadequate suppression of the inflammatory response following stimulation by an inciting agent; or (c) genetically inherited abnormalities in immune regulation (6). Investigations into the etiology of sarcoidosis have centered on identification of an infectious etiology. The increased incidence of cases presenting in the spring, associations with professions such as nursing, and increased prevalence in regions within a country all provide epidemiologic support for an infectious etiology (19-22). So far no infectious agent has been identified (12). Investigations into specific HLA types have failed to identify HLA markers consistently associated with an increased incidence of sarcoidosis (23). Recent studies by Wallaert et al. (24) suggest that sarcoidosis may result from a common disturbance in the mucosal immune system. They showed an increase in jejunal permeability using 51Cr-ethylenediaminetetraacetate in patients with active pulmonary sarcoid disease but with normal intestinal morphology. This increase in intestinal permeability approached that seen in patients with active Crohn's disease, but was significantly higher than the levels seen in inactive sarcoidosis, inactive Crohn's disease, or tuberculosis (24). Because of a clinical association between sarcoidosis and celiac disease, McCormick et al. (25) evaluated patients with sarcoidosis for IgG antibodies to α-gliadin. They found increased antibody titers to α-gliadin in 40% of their patients. They also demonstrated an increase number of jejunal intraepithelial lymphocytes when compared with normal controls despite the presence of normal morphology at endoscopy. Therefore, it is possible that a non-IgE-mediated sensitivity to an environmental agent may be responsible for initiating the granulomatous reaction noted in sarcoidosis. The seasonal, regional, and environmental clustering of sarcoid cases could be explained by seasonal variations in pollen counts, pollution indexes, and dietary habits. In summary, we present the first case of an adolescent with intestinal sarcoidosis. This diagnosis should be considered in patients with granulomatous lesions of the intestinal tract since the treatment should be tailored to maximize medical therapy, avoiding surgical procedures when possible.FIG. 1: . Cranial CT scan revealing a left periorbital mass measuring 1.1 × 0.9 cm located lateral and posterior to the orbit (arrow).FIG. 2: . Barium column on upper gastrointestinal series displaying intraluminal narrowing of the second portion of the duodenum (arrow). The duodenal lumen measured 4 mm in diameter on this contrast study. The more normal-appearing third portion of the duodenum measured 25 mm in diameter.FIG. 3: . Abdominal CT scan revealing an annular constricting lesion in the second portion of the duodenum (arrow).FIG. 4: . Histologic examination of tissue obtained from duodenal biopsy displaying superficial noncaseating granulomas (arrowhead) and marked lymphocytic inflammatory infiltrate.