Background Rare diseases (RD) like akute porphyrias (APs) present a particular challenge for emergency physicians (EP), as their acute symptoms are usually nonspecific and resemble common clinical presentations. This is compounded by low awareness and limited training of EP regarding RD, often leading to patients with RD being discharged without an accurate diagnosis. Consequently, despite the availability and necessity of targeted diagnostic and treatment options, RD patients may experience further complications and fatal outcomes. This study aimed to characterise patients with RD, such as APs, in the ED and to raise awareness of the problem of unrecognised rare but treatable diseases in the ED.

Methods The BEAWARE study conducted from July 2023 to June 2024 surveyed patients with RD throughout the German-speaking area, focusing on acute symptoms and presentations in the ED. A select group of RD, including AHP, was chosen to meet the following criteria: (a) causing acute symptoms, (b) diagnosable in the ED for adolescents or adults and (c) availability of therapeutic options. In addition, Embase and MEDLINE were searched up to November 2023 in a systematized literature review of articles on the clinical characteristics of patients with AHP in the ED.

Results A total of 147 RD patients (15 with APs) participated in the survey. Except for one patient, all AP patients (93.3%) reported that they did present to the ED prior to diagnosis. 8/14 of AP patients presented to the ED 1–2 times, 4/15 3–5 times, 1/15 11–20 times and 1/15 more than 20 times with symptoms of their later diagnosed AP.

Of 327 identified articles, 3 could be included that described the clinical presentation of 59 AP patients in the ED. The most common symptoms were abdominal pain (53/59) and neurological symptoms (confusion, paresis, numbness of the extremities, and seizures). The main reported trigger factors included menstrual cycle (28/36) and medication (8/49). Imaging typically yielded unremarkable results. Vital signs were within normal ranges for most patients and hyponatremia was observed in 32/46 patients. The patients‘ outcomes ranged from hospital release after two days to respiratory paralysis (in 3/59 patients) followed by three months of recovery and death in one patient due to a delay in diagnosis for a month.

Discussion and Conclusion Patients with APs frequently present to the ED prior to diagnosis and remain often undiagnosed for several visits. The sometimes serious and even fatal consequences emphasize the need for immediate diagnosis and treatment of APs in the ED.

Awareness and knowledge of rare diseases such as APs should be increased in the emergency department. So far, little is known in the literature about the presentation of AP patients in the emergency department. Perhaps AI-supported algorithms can support rapid diagnosis in the future.