Gastric Sarcoidosis Masquerading as Gastroesophageal Reflux Disease: A Case of Diagnostic Uncertainty and Conservative Management

Introduction

Sarcoidosis is a rare systemic disease characterized by non-caseating granulomas [1]. It primarily affects the lungs and intrathoracic lymph nodes in approximately 90% of cases, but any organ or tissue can be involved [2]. Although poorly understood, the pathophysiology is believed to involve a complex immune response influenced by multiple factors, including exposure to endogenous and exogenous antigens, such as beryllium, silica dust, or microbial agents, in genetically susceptible individuals [3]. The immunopathogenesis involves antigen-presenting cells that process these antigens and present them to CD4+ T cells, leading to activation of type 1 helper T cells and increased production of proinflammatory cytokines, such as interferon-γ, tumor necrosis factor-α, interleukin-2, and interleukin-12 [3]. This effector CD4+ T-cell response persists because of impaired regulatory T-cell function involving interleukin-10 and transforming growth factor-β, resulting in an exaggerated immune reaction. Such immune dysregulation activates additional macrophages and promotes the formation of non-caseating granulomas, ultimately progressing to fibrosis and organ dysfunction [4]. Diagnosing sarcoidosis remains challenging because of its variable presentation. It is considered a diagnosis of exclusion, requiring 3 criteria: a compatible clinical and radiologic presentation, histologic evidence of non-caseating granulomas (except in specific syndromes such as Löfgren syndrome and Heerfordt syndrome), and exclusion of other granulomatous diseases, including infections or malignancies [1,4]. Treatment decisions are individualized and must balance disease severity, risk of organ damage, quality of life, and medication toxicity. Guidelines recommend corticosteroids as first-line treatment for sarcoidosis. Immunomodulators such as methotrexate should be considered early in patients requiring long-term therapy or those unable to taper corticosteroids. In refractory cases, tumor necrosis factor-α inhibitors (infliximab, adalimumab) are recommended, with or without immunomodulators [4].

Gastrointestinal (GI) sarcoidosis is uncommon, representing approximately 0.1% to 0.9% of all sarcoidosis cases [5]. GI sarcoidosis mainly involves the upper GI tract, particularly the gastric antrum, and may present as part of a systemic condition or, less frequently, as an isolated finding [6]. Most cases are asymptomatic and are discovered incidentally during endoscopy. Fewer than 1% of patients experience symptoms. When symptoms occur, they are often nonspecific and variable, including gastroesophageal reflux disease (GERD), dyspepsia, weight loss, early satiety, GI bleeding, obstruction, or perforation [6]. Endoscopic findings can mimic malignancy; confirmation of non-caseating granulomas by histopathology is essential for diagnosis after excluding other granulomatous diseases, such as infections (tuberculosis or fungal infections), Crohn’s disease, or drug-induced sarcoidosis [7].

The association between gastric sarcoidosis and GERD is an underexplored link between a rare systemic disorder and a common condition. This relationship introduces diagnostic and treatment uncertainties that are not well addressed in the current literature. We present a case that illustrates these clinical challenges and emphasizes the complexity of management in the context of a possible association between GERD and gastric sarcoidosis. To facilitate clinical decision-making, we developed a systematic, algorithm-based approach for evaluating and managing patients who present with GERD in the context of established gastric sarcoidosis. This framework aims to guide clinicians through the diagnostic and therapeutic considerations unique to this clinical scenario and underscores the need for clearer guidelines concerning management of GERD in patients with sarcoidosis.

Case Report

A 48-year-old White man with a medical history of sarcoidosis was referred to gastroenterology for endoscopic evaluation of GERD and nonspecific chest pain. Seven years earlier, he had been diagnosed with pulmonary sarcoidosis and treated with corticosteroids, achieving a good clinical response after a 4-week course. He had remained in remission since that time. His only other medical condition was GERD, diagnosed 8 years earlier and managed with omeprazole 20 mg daily. Over the preceding 3 months, he had begun experiencing non-exertional chest pain, with unremarkable findings on a comprehensive cardiac evaluation. He reported good symptom relief with omeprazole 20 mg on most days; however, his Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) questionnaire score was 29, indicating a moderate symptom burden and noticeable impact on quality of life. The patient denied dysphagia, odynophagia, GI bleeding, unintended weight loss, or other alarm features. There were no symptoms suggestive of active systemic sarcoidosis, including fatigue, fever, night sweats, or cough. He also denied recent or prior use of tobacco, alcohol, or illicit substances. Vital signs were normal, and physical examination observations were unremarkable. Routine blood test results, comprehensive metabolic panel findings, and inflammatory markers were within normal limits. Chest radiography findings were unremarkable; no parenchymal abnormalities or hilar lymphadenopathy were noted.

Esophagogastroduodenoscopy showed grade A esophagitis in the lower third of the esophagus (Figure 1). Further visualization revealed a 6-mm papule with a nonspecific appearance in the gastric antrum (Figure 2). A tissue sample was obtained – in accordance with American Society for Gastrointestinal Endoscopy guidelines – because the lesion could represent various pathologies, including benign (hyperplastic, adenomatous, or inflammatory) polyps, granulomatous inflammation (infectious, Crohn disease, or sarcoidosis), or, rarely, neoplastic lesions [8]. The lesion was biopsied using standard cold biopsy forceps for diagnostic purposes. Histopathologic examination demonstrated chronic gastritis with a well-formed non-caseating granuloma in the lamina propria and chronic inflammatory cells in the surrounding mucosa (Figure 3). Acid-fast bacilli and periodic acid-Schiff staining results were negative, excluding mycobacterial and fungal organisms (Figure 4). The patient was advised to increase omeprazole to 40 mg daily, which reduced his GERD-HRQL score from 29 to 10 on reassessment 2 weeks later. He was also referred to a rheumatologist, who recommended that further treatment was unnecessary given his clinically quiescent disease and GERD-related symptom improvement in the context of gastric sarcoidosis.

At a 3-month follow-up visit, the patient’s symptoms remained well controlled, as reflected by a GERD-HRQL score of 8. Therefore, repeat endoscopic assessment was considered unnecessary.

Discussion

This case illustrates a rare instance of gastric sarcoidosis discovered incidentally during endoscopy for GERD and atypical chest pain in a patient with inactive pulmonary sarcoidosis. Population-based data suggest that patients with sarcoidosis have a higher risk of upper GI events relative to matched controls (hazard ratio 1.90, 95% confidence interval 1.27–2.83) [9]. Rather than clarifying the clinical picture, the unpredictable relationship between pulmonary and gastric sarcoidosis – where gastric involvement can occur before, during, or after pulmonary disease and may be asymptomatic or subclinical – underscores why the finding of gastric sarcoidosis in our patient with GERD posed additional diagnostic and treatment challenges.

Because the patient’s endoscopic findings were consistent with Los Angeles (LA) grade A esophagitis in the distal third of the esophagus (Figure 1), we decided to escalate his proton pump inhibitor (PPI) dose from 20 mg to 40 mg daily, in accordance with established American College of Gastroenterology (ACG) treatment guidelines for LA grade A esophagitis. The guidelines recommend standard-dose PPI therapy for 8 weeks for patients with mild esophagitis (LA grade A/B) [10]. This classification has diagnostic and treatment implications, considering a recent ACG consensus statement that LA grade A esophagitis alone may be insufficient for a definitive diagnosis of GERD; around 17.6% of LA grade A cases show objective GERD on pH-impedance testing [10]. Such diagnostic uncertainty was especially relevant in the present case, where it was challenging to distinguish between typical GERD and sarcoidosis-related gastric dysfunction.

Although no direct pathophysiologic mechanism has been established for GERD in patients with gastric sarcoidosis, proposed theories include granulomatous inflammation leading to esophageal dysmotility, impaired motility, and lower esophageal sphincter dysfunction [5]. Additionally, infiltration of the esophageal wall or nerve plexus may impair esophageal clearance, predisposing patients to reflux [11]. In our case, the presence of gastric sarcoidosis suggests that sarcoidosis contributed to the patient’s GERD; however, this attribution is not definitive. A diagnosis of GERD preceding pulmonary sarcoidosis and the presence of grade A esophagitis responsive to an increased dose of omeprazole support typical GERD. Conversely, the presence of non-caseating granulomas and coexisting gastritis indicates that local sarcoid activity might have disrupted gastric mucosal physiology. Without pH-impedance testing or clear improvement with immunosuppressive therapy, we cannot conclusively attribute the patient’s GERD to sarcoidosis.

There is no single sensitive or specific biomarker for sarcoidosis. Endoscopy with biopsy remains the primary tool for excluding other causes of non-caseating granulomas, given that sarcoidosis is a diagnosis of exclusion [6]. Similarly, there are no standardized guidelines for the treatment of gastric sarcoidosis; management is often extrapolated from general sarcoidosis protocols [4]. In such protocols, corticosteroids are recommended as first-line therapy to control inflammation [4]. For GERD in patients with sarcoidosis, management should begin with lifestyle modifications, such as weight loss, smoking cessation, and dietary changes [6]. After initiation of these measures, clinicians should evaluate whether GERD symptoms are caused by typical reflux disease or related to sarcoid inflammation, using studies such as pH-impedance testing. In prior reports, a few patients with gastric sarcoidosis and reflux symptoms demonstrated improvement through conservative management alone, whereas others required PPI therapy without systemic corticosteroids [12,13]. Furthermore, many patients have required immunosuppressive therapy when symptoms were attributed to active sarcoid inflammation or did not improve with PPIs [4]. However, corticosteroid use requires caution because reports suggest that corticosteroids can reduce lower esophageal sphincter tone and increase gastric acid secretion, which could precipitate or worsen GERD [4]. Considering the variability in clinical response, treatment of GERD in patients with sarcoidosis requires an individualized, multimodal, and multidisciplinary approach that balances standard GERD management with the potential need for systemic corticosteroids. Our decision to pursue conservative management is notable given the biopsy-confirmed diagnosis of gastric sarcoidosis. In most reported cases, histologically confirmed gastric involvement has prompted initiation of systemic corticosteroids, even in the absence of clear symptoms [6]. The present case suggests that histologic gastric involvement alone is insufficient to justify immunosuppressive therapy if the patient’s clinical status is stable, inflammatory markers are normal, and GERD symptoms improve with increased PPI dosing. This distinction between histologic evidence and clinically active disease is important for efforts to avoid unnecessary corticosteroid use. Further research is needed to determine the most effective treatment strategies for this patient population.

To guide clinicians in considering diagnostic and therapeutic options in these scenarios, we developed a proposed treatment algorithm – along with surveillance recommendations and clinical pearls – for patients with GERD in the context of established gastric sarcoidosis (Figures 5, 6). Our approach incorporates core principles from the treatment algorithm proposed by Drent et al in 2021, including assessment of disease severity, determination of indications for treatment initiation, stepwise therapeutic escalation from corticosteroids to steroid-sparing agents, and emphasis on multidisciplinary care [4]. We expanded this framework to specifically address GERD-related gastric sarcoidosis, including GERD severity stratification, assessment of PPI responsiveness, esophageal pH-impedance testing to distinguish acid reflux from granulomatous inflammation, and treatment pathways based on evidence of active gastric sarcoid inflammation (Figures 5, 6).

Although the prognosis for isolated GI sarcoidosis is generally favorable, patients with systemic GI sarcoidosis have a persistent risk of disease progression. These patients may require extended management or surveillance with symptom monitoring, laboratory testing, or endoscopy due to the risk of life-threatening complications such as GI bleeding, obstruction, or perforation. In the present case, although the rheumatologist considered the patient’s sarcoidosis (including gastric involvement) to be clinically inactive, routine follow-up of inflammatory markers was recommended for monitoring.

Conclusions

This case emphasizes that gastric sarcoidosis can coexist with GERD; thorough clinicopathologic correlation, including endoscopic sampling and physiologic testing when feasible, is necessary before attributing causality. GERD related to sarcoidosis should be considered in the differential diagnosis when patients with a history of sarcoidosis exhibit reflux symptoms. Prospective studies and formal guidelines are needed to help clinicians navigate the diagnostic and therapeutic considerations specific to this clinical scenario. The decision to avoid immunosuppressive therapy was appropriate in the present case, given that the patient’s GERD symptoms responded well to omeprazole. Long-term surveillance with periodic symptom assessment and endoscopic evaluation remains important due to the risk of disease progression and life-threatening complications such as GI bleeding, obstruction, and perforation. This case adds to the limited literature addressing situations in which gastric sarcoidosis may be managed without immunosuppressive therapy.