RESEARCH ARTICLE. The Relationship between Sarcoidosis of Intrathoracic Lymph Nodes and Digestive System Diseases: A Comparative Observation

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1 ISSN Journal of Global Pharma Technology Available Online at RESEARCH ARTICLE The Relationship between Sarcoidosis of Intrathoracic Lymph Nodes and Digestive System Diseases: A Comparative Observation A.V. Medvedev Ph.D. (Medicine), Senior Researcher, Central Scientific Research Institute of Tuberculosis, Moscow, Russia. Abstract Background: The cases of sarcoidosis of intrathoracic lymph nodes often accompanied by various digestive system diseases have not received enough attention in medical publications. Therefore, the objective of this study is to explore the interrelatedness between the development of gastrointestinal disorders and pulmonary pathology. Materials and methods: The study included 79 patients with sarcoidosis of intrathoracic lymph nodes (ITLN), mean age 46.4±0.9, disease duration 6.8±0.4 years. The patients studied were divided into two groups: patients with ITLN sarcoidosis with gastrointestinal (GI) tract diseases, and people with ITLN sarcoidosis with no symptoms of gastrointestinal tract diseases. All patients underwent laboratory and instrumental examination. Results: Diseases of the digestive system were found in 19 patients with ITLN sarcoidosis. Newly diagnosed digestive system diseases were observed in four patients: one patient with duodenal, three patients with gastroesophageal reflux disease (GERD). Exacerbation of previously diagnosed diseases was recorded in fifteen patients; most often it was exacerbation of chronic gastritis and chronic duodenal (five cases each), in three patients it was exacerbation of chronic cholecystitis, in two patients exacerbation of chronic pancreatitis and chronic gastric was detected. Conclusion: The development of gastrointestinal diseases coincides in time with the development of sarcoidosis or occurs under conditions of its treatment. In patients with sarcoidosis who underwent therapy of this disease, gastrointestinal diseases were observed in 55.5% of patients, in patients with recurrent, progressive course of sarcoidosis they were observed 1.4 times more often than in those with steady course of sarcoidosis. Keywords: Sarcoidosis of Intrathoracic Lymph Nodes (ITLN Sarcoidosis) Gastrointestinal Diseases- Digestive System Pathology. Background Digestive system diseases in case of sarcoidosis of intrathoracic lymph nodes, pulmonary sarcoidosis and ITLN sarcoidosis are not well-studied. Diseases of salivary glands are found in 6% of patients with sarcoidosis [1], esophageal diseases occur in 0.5-1% of cases [2], small intestine diseases are diagnosed in % of patients [3, 4]. Non-caseating epithelioid granulomas in the gastric mucosa are found in 1-2% of patients with sarcoidosis [5], sarcoid affection of lungs and liver is detected in 15-70% of patients [6]. Digestive system diseases may occur as comorbidity or sarcoidosis treatment complications [7]. Outcomes of sarcoidosis with extrathoracic manifestations are various: from catarrhal inflammation of the salivary glands [8] to ative lesions of the antrum [9] and obstruction of the large intestine [10]. Different frequencies of sarcoid lesions of the gastrointestinal tract, different outcomes of this disease necessitate studying the problem of combined lesions of the gastrointestinal tract in patients with pulmonary sarcoidosis and sarcoidosis of intrathoracic lymph nodes. The features of the relationship of gastrointestinal disorders in sarcoidosis, possibility of mutual influence of these conditions are still not studied, which makes it relevant to examine this issue further. Thus, the objective of this research is to study the relationship between simultaneous ITLN sarcoidosis and gastrointestinal diseases , JGPT. All Rights Reserved. 66

2 Criteria for Inclusion in the Study Adult patients of both sexes between 15 and 70 years old. Patients with radiographic pattern characteristic for ITLN sarcoidosis and morphological confirmation of the diagnosis (detection of epithelioid cell granulomas). Patients consent to undergo the study, including invasive studies (esophagogastroduodenoscopy, colonoscopy). Criteria for Exclusion Anamnesis including one of the following diseases: bronchiectasis, fibrosing alveolitis, exogenous allergic alveolitis, kyphosis and scoliosis of the chest, pulmonary tuberculosis, cancer of any localization. Exacerbation of a chronic disease (chronic tonsillitis, chronic pyelonephritis, etc.) that can distort the results of the study. Fungal lung diseases. Thromboembolism of small branches of the pulmonary artery. Disseminated processes unclarified at the time of screening. Research Methods Clinical and biochemical blood tests, sputum examination, ECG, chest X-ray, spirometry, body plethysmography, the study of the diffusion capacity of lungs, CT of chest organs, bronchoscopy with the analysis of bronchoalveolar lavage, scintigraphy with gallium citrate 67 Ga, esophagogastroduodenoscopy, colonoscopy, ultrasonic examination of abdominal cavity. The study involved 79 patients with sarcoidosis of intrathoracic lymph nodes with or without gastrointestinal pathology: 38 men, 41 women. Their average age was 46,4±0,9. We conducted dynamic observation within twenty-four months. To evaluate the effect of the combination of sarcoidosis of intrathoracic lymph nodes on the development of digestive system diseases, patients were divided into four groups depending on the terms of the development of pulmonary and gastroenterological diseases. Group 1: Gastrointestinal tract (GIT) disease develops before respiratory system disease and does not manifest simultaneously with this respiratory system disease. Group 2: Gastrointestinal tract disease develops before respiratory system disease and manifests in the long term treatment of sarcoidosis or under sarcoidosis treatment conditions. Group 3: Gastrointestinal tract disease develops after the onset of respiratory system disease and manifests simultaneously with it. Group 4: Both diseases evolve simultaneously, the gastroenterological tract disease progresses in the long-term treatment of sarcoidosis and (or) under sarcoidosis treatment conditions. Anamnesis data (the time factor of digestive disease development before, after, or simultaneously with ITLN sarcoidosis), the peculiarities of the course of the gastrointestinal tract disease (its exacerbation or progression in the long-term treatment of sarcoidosis or under sarcoidosis treatment conditions), the reversibility of exacerbation of the digestive system disease under sarcoidosis treatment conditions were considered as the basis of assessment of the nature of sarcoidosis and gastrointestinal tract diseases combination. Thus, we evaluated the following possible relationships: Independent existence of gastrointestinal tract diseases and ITLN sarcoidosis; Mutual aggravation of these two diseases; Aggravation of respiratory disease in the presence of digestive system disease; Aggravation of gastroenterological disease in the course of treatment of respiratory disease. Results and Discussion In the study of 79 patients with ITLN sarcoidosis, the gastrointestinal tract disease was found in 19 patients (24.05%). We have studied 4 groups of patients with different terms of the development of sarcoidosis and the gastrointestinal tract disease , JGPT. All Rights Reserved. 67

3 The nature of digestive diseases in patients with sarcoidosis of intrathoracic lymph nodes is given in Table 1. A.V. Medvedev, Journal of Global Pharma Technology. 2017; 04(9):66-70 Table 1: Structure of digestive diseases in patients with ITLN sarcoidosis Digestive system Gastrointestinal Gastrointestinal tract Development of Development of diseases tract disease before disease before gastrointestinal gastrointestinal sarcoidosis and not sarcoidosis and tract disease after tract disease manifesting manifesting sarcoidosis and simultaneously simultaneously with simultaneously under manifesting with aggravation it sarcoidosis treatment simultaneously under sarcoidosis conditions with it. treatment conditions GERD (3.78%) Chronic gastritis 0 2 (2.53%) 2 (2.53%) 1 (1.26%) Newly diagnosed peptic Aggravation of gastric (1.26%) Newly diagnosed (1.26%) duodenal Aggravation of duodenal 0 2 (2.53%) 2 (2.53%) 1 (1.26%) Chronic pancreatitis 1 (1.26%) Chronic cholecystitis 3 (3.78%) Total 4 (5.04%) 4 (5.04%) 4 (5.04%) 7 (8.82%) In the first group of patients, in four cases (5.04%) the anamnesis included an indication of hepatobiliary system diseases (chronic cholecystitis and chronic pancreatitis). During the entire period of observation, these diseases had no clinical manifestations. It is noteworthy that in most patients (15 patients) clinical manifestations of gastrointestinal tract diseases were recorded with the simultaneous development of sarcoidosis and under its treatment conditions (patients of groups 2-4). In 11 of these fifteen patients (or 73.3%), the onset of gastrointestinal tract diseases coincided with respiratory system disease or developed after its occurrence. Mainly, in eight patients, organic diseases of the digestive system were diagnosed (stomach and duodenal, chronic gastritis); three patients had functional impairment of the cardial-esophageal zone, gastroesophageal reflux disease in particular. Newly diagnosed digestive system diseases were observed in four patients; one patient was diagnosed with duodenal, three patients had gastro-esophageal reflux disease. Exacerbation of previously diagnosed diseases was recorded in fifteen patients; most often it was exacerbation of chronic gastritis and chronic duodenal s (five cases), three patients had exacerbation of chronic cholecystitis, two patients suffered from exacerbation of chronic pancreatitis and chronic gastric. According to the data obtained, hepatobiliary system diseases (chronic cholecystitis, chronic pancreatitis) did not have temporal relationship with sarcoidosis. These diseases evolved before sarcoidosis and were not clinically manifested in the process of its treatment, being independent gastroenterological diseases. Diseases of the upper gastrointestinal tract (gastro-esophageal reflux disease, duodenal, chronic gastritis) had temporal relationship with sarcoidosis; these diseases developed simultaneously with sarcoidosis under its treatment conditions. Aggravation of these gastrointestinal diseases coincided with the intensification of sarcoidosis activity. The studied patients with ITLN sarcoidosis had various courses of the disease. In 29 patients (36.7% of cases), sarcoidosis was diagnosed as an accidental discovery during prophylactic medical examination. In this case, X-ray of twenty-four patients revealed bilateral lymphadenopathy; in five patients it was unilateral lymphadenopathy. Of these, 14 patients (17.7%) had spontaneous regression, with the normalization of X-ray pattern, and did not require medical treatment , JGPT. All Rights Reserved. 68

4 In 15 patients (18.9%), no radiographic symptoms of regression were observed, so drug therapy with fenspiride, tocopherol was assigned for three months. After the treatment, the normalization of radiological changes was achieved (regression under sarcoidosis treatment conditions). In 38 patients (48.1%), the course of sarcoidosis was stable after previously conducted treatment. Within two years prior to inclusion in the study and during followup, no drug therapy was administered to these patients. In 10 patients with sarcoidosis of intrathoracic lymph nodes (12.6%), whose previous treatment resulted in the disappearance of intrathoracic lymphadenopathy, after 9.3±0.3 months the clinical symptoms (cough, shortness of breath, weakness) were observed again; CT scans of chest organs demonstrated an increase in the lymph nodes. The status of these patients was assessed as undulating recurrent course of sarcoidosis. Sarcoidosis therapy was resumed for them (systemic corticosteroids at a daily dose of 14.5±0.5 mg/day equivalent to prednisolone, azathioprine, 98.8±0.1 mg/day, extracorporeal therapies). The terms of treatment were 5.9±0.1 months. Two patients with sarcoidosis of intrathoracic lymph nodes (2.53%) had the symptoms of the process progression i.e. increased respiratory symptoms (cough, shortness of breath), quantitative increase in the size of intrathoracic lymph nodes, the emergence of bilateral dissemination. One of the patients had nodal erythema of shins, another had eye involvement (dry iridocyclitis), increase in cervical lymph nodes. The condition of the patients was regarded as progressive course of sarcoidosis. These patients underwent three-month therapy with systemic corticosteroids (22.6±0.3 mg/day equivalent to prednisone, azathioprine, 99.2±0.4 mg/day, extracorporeal therapies). Thus, due to a favorable outcome of stable course of sarcoidosis, most of the 79 patients studied (52 patients or 65.8%) did not require drug therapy. A significant number of the patients (27 patients or 34.2%) with the need for sarcoidosis treatment, had gastrointestinal tract diseases as comorbidity (15 cases in 27 patients, or 55.5%). The incidence of digestive system diseases in various cases of sarcoidosis of intrathoracic lymph nodes is shown in Table 2. Table 2: Incidence of digestive system diseases in various cases of sarcoidosis of intrathoracic lymph nodes (n =79) Digestive diseases system Spontaneous regression, n = 14 Regression under sarcoidosis treatment conditions, n = 15 Steady course of sarcoidosis, n = 38 Recurrent course, n = 10 Progressive course, n = 2 GERD (2.53%) 1 (1.26%) Chronic gastritis 0 2 (2.53 %) 0 3 (3.78%) 0 Newly diagnosed peptic Chronic peptic (1.26%) 0 Newly diagnosed (1.26 %) duodenal Chronic duodenal 0 2 (2.53%) 0 1 (1.26%) 2 (2.53%) Chronic pancreatitis (1.26%) 0 0 Chronic cholecystitis (3.78%) 0 0 Total 0 4 (5.04%) 4 (5.04%) 7 (8.82%) 4 (5.04%) Table 2 demonstrates that in patients with sarcoidosis who did not receive medical treatment (in case of spontaneous regression of sarcoidosis with its steady course), digestive system diseases (chronic cholecystitis, chronic pancreatitis) were observed in four of 52 patients (7.7%). In patients with sarcoidosis with administered therapy of this disease, gastrointestinal tract diseases were observed in more than half of the patients (15 of 27 patients or 55.5%) , JGPT. All Rights Reserved. 69

5 There was a trend of increasing incidence of diseases of the digestive system, depending on sarcoidosis activity: in patients with recurrent, progressive course of sarcoidosis, they were found 1.4 times more often than in cases of steady course of sarcoidosis. The most common were the diseases of the upper gastrointestinal tract: gastro-esophageal reflux disease comprised 3.78%, exacerbation of chronic gastritis and chronic duodenal accounted for 6.3% each. Conclusions Diseases of the digestive system were found in 24.05% of patients with ITLN sarcoidosis. They are represented by newly diagnosed diseases and exacerbation of previously diagnosed gastrointestinal tract diseases. Newly diagnosed diseases were found in 6.3% of patients: 1.3% had duodenal, 5.06% had gastro-esophageal reflux disease. Exacerbation of previously diagnosed diseases was found in 17.73% of the patients: chronic cholecystitis in 3.8% of patients, exacerbation of chronic gastritis, chronic forms of ous disease in 6.3% of patients. The incidence of gastrointestinal tract diseases depends on the drug burden; in patients with sarcoidosis which was treated, gastrointestinal tract diseases were found in 55.5% of patients; in the absence of drug therapy of sarcoidosis they were diagnosed in 7.7% of patients. In case of progressive, recurrent course of ITLN sarcoidosis, gastrointestinal tract diseases occur 1.4 times more often than in patients with steady course of sarcoidosis. The most common were the diseases of the upper gastrointestinal tract such as gastroesophageal reflux disease, exacerbation of chronic gastritis and chronic duodenal. Abbreviations CT: computed tomography ECG: electrocardiography GERD: gastroesophageal reflux disease GI: gastrointestinal GIT: gastrointestinal tract ITLN: intrathoracic lymph node(s) References 1. James DG, Sharma OP. Parotid gland sarcoidosis. Sarcoidosis Vac. Diffuse Lung Dis. 2000; 17(1): Lukens FJ, Machicao VI, Woodward TA, De Vault KR. Esophageal sarcoidosis an unusual diagnosis. J. Clin. Gastroenterol. 2002; 34(1): Tsibouris P, Kalantzis C, Alexandrakis G, et al. Capsule endoscopy findings in case of intestinal sarcoidosis. Endoscopy. 2009; 41 Suppl 2: Marie I, Sauvetre G, Levesque H. Small intestinal involvement revealing sarcoidosis. QJM. 2010;103 (1): Hermandez CJ, Gonzalez BS, Alvarez LM, Lisboa BC. Pulmonary and gastric sarcoidosis report of one case. Rev. Med. Clin. 2009; 137(7): Blich M, Edoute Y. Clinical manifestations of sarcoid liver disease. Gastroenterol. Hepatol. 2004; 19 (7): Vladimirova EB, Romanov VV, Shmelyov EI. Systemic manifestations of sarcoidosis. Problems of tuberculosis. 2006; 3: (in Russian) 8. Mandel L, Wolinsky B, Chalom EC. Treatment of refractory sarcoidal parotid gland swelling in a previously reported unresponsive case. J. Am. Dent. Assoc. 2005; 136 (9): Akiyama T, Endo H, Inamori M, et al. Pulmonary and gastric sarcoidosis with multiple antral s. Endoscopy. 2009; 41 Suppl 2: Ostor AJ, Moran H, Wick IP. Gross abdominal lymphadenopathy in sarcoidosis. Intern. Med. J. 2002; 32(8): , JGPT. All Rights Reserved. 70