Department of Surgery, Meharry Medical College, Nashville, Tennessee 37208.

Upper gastrointestinal (GI) bleeding due to peptic ulcer disease (PUD) has several etiologies, with H. pylori and NSAID’s as predominate underlying causes.  There are other, more unusual causes of PUD, such as gastric sarcoidosis, of which there are only a few documented cases. Sarcoidosis typically presents with pulmonary and other systemic manifestations, and rarely affects the gastrointestinal (GI) tract, with the gastric mucosa most commonly involved [1]. A nationwide population-based study found a significant difference in the clinical presentation between African Americans and Caucasians, with African Americans generally experiencing more extra-pulmonary sarcoidosis, worse prognosis, and an age-adjusted mortality rate that is 12 times higher than Caucasians [2].  Although about 10% of patients with systemic sarcoidosis will have positive gastric pathology, only about 0.1 to 0.9% of these patients will be symptomatic [3,4].  Of the symptomatic patients, approximately 25% present with upper GI bleeding [5].  In a case-control study of 25 cases of gastric sarcoidosis, 26% presented with ulcerations, and 17% had hematemesis, making these key clinical features of gastric involvement [6]. Typically, a diagnosis of gastric sarcoid warrants further investigation to rule out pulmonary or disseminated disease since one of these is usually a prerequisite for gastric involvement [7,8]. The case described in this report is an unusual presentation of upper gastrointestinal bleeding due to gastric sarcoid without any previous history of sarcoidosis or other granulomatous disease.

A 38-year-old Caucasian female with a history of chronic obstructive pulmonary disease, seizure disorder, and tobacco abuse presented to the emergency room with a one-year history of abdominal pain which had worsened in the previous month.  She also complained of hematemesis, weakness, fatigue, dizziness, and a seven-pound weight loss. Her examination was notable for epigastric tenderness without guarding and mild lower extremity edema. Laboratory examination was significant for a hemoglobin (Hg) of 6.8 gm/dL. 

Two years following the gastrectomy she presented with complaints of epigastric pain and early satiety. An EGD and contrast study demonstrated narrowing at the gastrojejunostomy anastomosis. A Roux en Y revision of the anastomosis was performed to alleviate her symptoms. No evidence of sarcoid was demonstrated in the surgical specimen. Upon follow-up the patient has remained well without any symptoms of recurrent gastric disease.

It is unusual to diagnose gastric sarcoid without a history of disseminated disease, but there are rare reports of isolated gastric sarcoidosis [1] without extra-intestinal involvement. Gastric granulomatous disease was previously classified into three groups by Fahimi et al. [9]: cases of disseminated sarcoidosis, regional enteritis with gastric involvement, and isolated granulomatous gastritis without disseminated sarcoidosis or small bowel disease.  Our case appears to belong to the third group, as the clinical and pathological findings in this case are consistent with gastric sarcoidosis [Fig.1]. Of the different types of gastric sarcoidosis, our patient’s presentation is most consistent with ulcerative gastric sarcoidosis, a disease associated with upper GI bleeding, epigastric pain, and pyloric ulcers that often result in gastric outlet obstruction [10]. 

 

Symptomatic gastric sarcoidosis is a diagnosis of exclusion requiring extensive work up.  A definitive diagnosis can be determined by three components: biopsy evidence of non-necrotizing granulomas in the symptomatic or incident organ, exclusion of other causes of granulomatous disease, and clinical, radiological and optimally histopathologic evidence of sarcoidosis in at least one other organ [11]. Patients will most often present with dull, burning or cramping and often post-prandial epigastric pain as chief complaints, and may also complain of weight loss, nausea, heartburn, vomiting, and hematemesis [1,3,12]. Manifestations of GI sarcoidosis are usually associated with peptic ulcerations or a narrowed gastric lumen due to granulomatous inflammation, as seen with our patient, and related fibrosis of the gastric wall, leading to decreased peristalsis [13]. In this case, the diagnosis of gastric sarcoid is primarily one of exclusion with evidence of non-necrotizing granulomas. Upper endoscopy is performed preferably to imaging studies [14] and may reveal nodular changes, greater or lesser curvature deformities, hyperemia, benign or malignant-appearing single or multiple ulcerations, acute erosive gastritis, mucosal rigidity and thickened gastric folds [14-16]. Contrast radiography may demonstrate antral deformity or pyloric narrowing, a rigid stomach, and segmental mucosal abnormalities [9]. Gastric sarcoid has also been reported to resemble the linitis plastica variety of gastric cancer on radiological imaging and even at operation [16]. As these findings are non-specific, mucosal biopsies are necessary to rule out non-infectious and infectious etiologies [17].

As previously mentioned, this is a diagnosis of exclusion, and much of the work up points to gastric sarcoidosis as the underlying cause of the intractable upper GI bleeding in our patient. Duodenal biopsy showed a negative Giemsa stain for H. pylori and there was no clinical evidence of Crohn’s disease. Further, regarding the detection of granulomas on biopsy, intestinal sarcoidosis usually involves only the mucosa, as seen with our patient, whereas the cobblestone inflammation in Crohn’s disease can be transmural [19]. While duodenal biopsies revealed atrophy consistent with celiac’s, serology was negative.  Serum gastrin level was 366 pg/mL, which may have been elevated due to acid suppression therapy, but the value was not high enough for a definitive Zollinger-Ellison disease diagnosis.  Acid hypersecretion is associated with hypercalcemia, but her calcium levels were consistently normal. Gastric lymphoma can also present with hematemesis and have similar pathology to granulomatous gastritis, however in this case, malignancy was ruled out via histologic examination of surgical specimen, which revealed multiple benign gastric ulcers with normal resection margins. The deepest ulcer, found at 4 cm from the resection margin, measured 1.5×1 cm in diameter with a depth of approximately 0.6 cm. Lastly, our patient was taking Dilantin which can cause granulomas, however no incidents of aggressive peptic ulcer disease related to use of the drug have been reported.

This unusual case illustrates the characteristics of isolated gastric sarcoidosis with hematemesis, demonstrates the progression of this rare disease, and the emphasizes need for prompt surgery for medical treatment failure. It is important for physicians to identify the signs and symptoms, laboratory and radiologic evidence, and pathologic findings associated with gastric sarcoidosis in order to establish a working knowledge of the disease and to provide opportunities for more in-depth studies. Early surgical intervention should be considered in cases of isolated gastric sarcoidosis with ulcerations and hematemesis that do not resolve by antacid, proton pump inhibitor and/or steroid therapy to prevent life threatening upper GI hemorrhage.

Contributors: AB: manuscript writing, patient management; LLD: manuscript editing, patient management. AB will act as a study guarantor. Both authors approved the final version of this manuscript and are responsible for all aspects of this study.

Funding: None; Competing interests: None stated.