Common features of rare disease patients in the emergency department: a systematised literature review

Patients with rare diseases (RD) may present to the emergency department (ED) with an acute manifestation of an undiagnosed RD. If not identified, some of these patients may suffer from increased morbidity, mortality and worse outcomes compared to patients with more common diseases. Unfortunately, patients with RD often present with common symptoms, e.g. abdominal pain, making it even more difficult for ED physicians to identify those patients. Thus, strategies are needed to determine when certain RD should be suspected in the ED. We aimed to identify common features of RD through a systematised literature review of a predefined set of RD. Embase and MEDLINE were searched for eligible studies published in all years up to November 2023. Studies reporting clinical characteristics of patients who presented to the ED with one out of a predefined set of eight RD were included: acute hepatic porphyria, Fabry disease, familial Mediterranean fever, hereditary angioedema, hereditary hemorrhagic telangiectasia, myasthenia gravis, paroxysmal nocturnal hemoglobinuria and thrombotic thrombocytopenic purpura. Clinical characteristics, symptoms and family history were extracted to explore potential common features. Database searches, title, abstract and full-text screening and data extraction were conducted by a single reviewer. Of the 4 732 articles identified, 18 were included in the review. For two RD no articles and for three RD only one article could be included. All but two prospective studies were retrospective chart reviews or case series reporting on small patient cohorts (n = 3 - 75 patients). The common features of patients were: age under 65 years, recurrent symptoms affecting multiple organ systems, normal or nonspecific findings in routine laboratory tests and imaging, presence of trigger factors and a positive family history of similar symptoms or RD. This review highlights the limited knowledge about RD in the ED setting. Some common features of RD patients were identified that could aid future research in developing risk stratification algorithms to facilitate early detection and treatment of RD in the ED. To our knowledge, this is the first literature review to explore the common features of patients with RD in the ED.