Differential Diagnosis for Nausea, Vomiting, Diarrhea, and Fever

Critical Life-Threatening Diagnoses to Exclude First

The American Diabetes Association defines diabetic ketoacidosis (DKA) by plasma glucose ≥250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, and positive ketones, which can present with nausea, vomiting, and abdominal pain in diabetic patients 2
Hyperosmolar hyperglycemic state (HHS) presents with plasma glucose ≥600 mg/dL, altered mental status or severe dehydration, and effective serum osmolality ≥320 mOsm/kg, and infection is a common precipitant 2
Intravenous rehydration with isotonic fluids is required when there is severe dehydration, shock, or altered mental status, according to the Clinical Infectious Diseases guidelines 1

Infectious diarrhea is the most common cause of acute nausea, vomiting, diarrhea, and fever, and should be the primary working diagnosis in this presentation, as stated by the Clinical Infectious Diseases journal 1
Stool work-up should include evaluation for blood, fecal leukocytes, C. difficile, Salmonella, E. coli, and Campylobacter in patients with fever or signs of inflammatory diarrhea, according to the Journal of Clinical Oncology 3
COVID-19 can present with nausea, vomiting, and diarrhea that predate respiratory symptoms, with up to 61% of outpatients experiencing GI symptoms, as reported by the Clinical Gastroenterology and Hepatology journal 4

Gastroparesis affects 20-40% of diabetic patients and presents with nausea, vomiting, and early satiation, and hyperglycemia itself causes gastric dysmotility, making blood glucose control essential in evaluating GI symptoms in diabetic patients, according to the American Diabetes Association 5

Systemic corticosteroids used for asthma exacerbations can cause nausea, vomiting, and hyperglycemia, as stated by the Intensive Care Medicine journal 6
SGLT2 inhibitors can precipitate DKA with glucose <200 mg/dL (euglycemic DKA), particularly with dehydration, reduced food intake, or infection, according to the Praxis Medical Insights guidelines 2

Assess hemodynamic status including blood pressure, heart rate, orthostatic changes, temperature, and mental status to identify volume depletion, ongoing losses, infection, or shock, as recommended by the Clinical Infectious Diseases journal 1
Obtain plasma glucose, complete metabolic panel with calculated anion gap, complete blood count, lactic acid, arterial blood gas (if glucose >250 mg/dL), and urinalysis with urine ketones, as stated by the Praxis Medical Insights guidelines 2

Adrenal insufficiency can present with nausea, vomiting, fever, hypotension, hyponatremia, and hyperkalemia, as reported by the Intensive Care Medicine journal 6
Thyroid storm (in undiagnosed hyperthyroidism) presents with fever, tachycardia, vomiting, diarrhea, and altered mental status, according to the American Family Physician journal 8

Do not attribute all GI symptoms to simple gastroenteritis in diabetic patients without checking blood glucose and assessing for hyperglycemic crisis, as warned by the Praxis Medical Insights guidelines 2
Do not delay treatment for severe dehydration while pursuing diagnostic work-up; begin isotonic fluid resuscitation immediately if hemodynamically unstable, as recommended by the Clinical Infectious Diseases journal 1
Recognize that approximately 10% of patients can present with concurrent DKA and HHS features, requiring aggressive management of both conditions, according to the Praxis Medical Insights guidelines 2