A Rare Case of Extra-Pulmonary Sarcoidosis With Only Initial Presentation of Hypercalcemia.

Sarcoidosis is a systemic disorder characterized by the aberrant development of granulomatous inflammation within various organs in the body. In over 90% of cases, sarcoidosis typically manifests initially in the intra-thoracic region, characterized by pulmonary involvement or mediastinal lymphadenopathy. It is rare for sarcoidosis to manifest exclusively as extra-thoracic involvement and even more rarely for hypercalcemia to be the only initial sign. We present a case of a 70-year-old female with hypercalcemia and elevated 1,25-dihydroxyvitamin D3 (1,25(OH)2 D) which raised the suspicion of a granulomatous disease. Granulomatous diseases increase levels of 1,25(OH)2 D via the abnormal expression of 1 alpha-hydroxylase enzyme; therefore, these conditions should be considered in the differential diagnosis when encountered with hypercalcemia. PET-CT showed increased FDG uptake in the reticuloendothelial system. An easily accessible inguinal lymph node biopsy was performed which revealed non-necrotizing granulomatous inflammation. Other causes of non-necrotizing granulomatous diseases, cancer, and lymphoma were ruled out, leading to sarcoidosis being considered as a possible diagnosis. When diagnosing sarcoidosis, other potential causes of granulomatous inflammation need to be ruled out definitively via laboratory findings, imaging, and tissue histopathology before initiation of treatment with steroids. Treatment with glucocorticoids remains the mainstay therapy of 1,25(OH)2 D-mediated hypercalcemia associated with sarcoidosis. The patient was accordingly treated with prednisone which led to the normalization of calcium and 1,25(OH)2 D levels within three weeks. Here, we discuss the clinical features and investigations of extra-pulmonary sarcoidosis for early diagnosis and management.

Disease modifying therapy and pregnancy outcomes in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVES: To report pregnancy outcomes among multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs). METHODS: We performed a retrospective chart review of articles published from June 1996 to May 2023. Additional information was acquired from the drug registries of individual pharmaceutical companies. A comparison was also made with pregnancy data of the general population using the World Health Organization database. Summary analysis was achieved using R statistical software (v3.6), and the overall prevalence of outcomes was estimated using a random effects model. RESULTS: A meta-analysis of 44 studies was conducted. Dimethyl fumarate had the highest prevalence of premature births at 0.6667% (SD:0.5236-0.7845). The highest rates of stillbirths and infant deaths (perinatal and neonatal) were observed with interferons at 0.004% (SD:0.001-0.010) and 0.009% (SD:0.005-0.0015), respectively. Cladribine had the majority of ectopic pregnancies (0.0234%, SD:0.0041-1217), while natalizumab had the highest prevalence of spontaneous abortions (0.1177%, SD:0.0931-0.1477) and live birth defects (0.0755%, SD:0.0643-0.0943).None of the outcomes were significantly different from those of the general population (p > 0.05), except ectopic pregnancy and spontaneous abortion (p < 0.001), where the odds were 0.665 (0.061-0.886) and 0.537(0.003-0.786), respectively. The pooled prevalence of MS relapses was 221% for a single episode (SD:0.001-0.714), 0.075% for more than one episode (SD:0.006-0.167), and 0.141% for at least one episode requiring steroids (SD:0.073-0.206) none of these reached clinical significance. CONCLUSION: Existing research suggests that DMT use in MS patients during pregnancy is generally considered safe. This study supports their utilization on a case-by-case basis. However, further primary research on this topic with clinical trials is warranted.

Early Definitive Diagnosis and Management of Incidental Neuroendocrine Tumors Found on Gastrointestinal Endoscopy.

Neuroendocrine tumors (NETs) are tumors that originate from neuroendocrine cells and can be found throughout the body but are most commonly seen in the gastrointestinal tract, pancreas, and lungs. There is an increase in the diagnosis of NETs due to advances in diagnostic modalities. Although mucosal tumors are easily visualized on upper GI endoscopic imaging, neuroendocrine tumors are often missed due to their deep mucosal origin with normal overlying mucosa. We first present the case of a 46-year-old woman with anemia and epigastric discomfort who was found to have an incidental submucosal mass in the duodenal bulb on esophagogastroduodenoscopy (EGD), which on endoscopic ultrasound (EUS) with a fine needle biopsy (FNB) showed a neuroendocrine tumor. Imaging with CT, however, failed to detect the presence of the mass in the duodenum. Furthermore, a DOTATATE scan showed only a nonspecific signal near the liver. The patient then underwent an EGD-guided, laparoscopic, robot-assisted transduodenal resection of the tumor, together with the removal of enlarged peritumoral lymph nodes. Pathology showed a well-differentiated neuroendocrine tumor of the duodenal bulb with metastasis to one lymph node, which was confirmed via immunohistochemistry staining. The second case is of a 51-year-old female who presented with occasional constipation and rectal pain and was found to have a rectal polypoid lesion on her colonoscopy, jumbo biopsies of which revealed a NET. An EUS done for staging and endoscopic mucosal resection (EMR) revealed a grade 1 well-differentiated NET on pathology, which was confirmed by immunohistochemistry staining. These cases stress the need for timely, definitive diagnosis and intervention. Here, we discuss the clinical features and investigations of neuroendocrine tumors for early diagnosis and management.